Showing papers in "Pharmacology, Biochemistry and Behavior in 1979"
TL;DR: Results suggest that dopaminergic nerve terminals in nucleus accumbens are necessary for both the acquisition and maintenance of d-amphetamine self-administration.
Abstract: Control rats initiate self-administration of d-amphetamine and achieve stable injection rates within 7-10 days. Rats in which dopamine nerve terminals in nucleus accumbens were destroyed by bilateral microinjections of 6-hydroxydopamine (6-OHDA) did not initiate self-administration of d-amphetamine when tested for as long as 19 days. In rats previously trained to self-administer d-amphetamine, 6-OHDA injections into nucleus accumbens abolished d-amphetamine self-administration. These results suggest that dopaminergic nerve terminals in nucleus accumbens are necessary for both the acquisition and maintenance of d-amphetamine self-administration.
462 citations
TL;DR: Several new lines of evidence suggest the existence of two or more distinct types of benzodiazepine receptors, in contrast to earlier results suggesting the presence of only one class of receptors.
Abstract: Several new lines of evidence suggest the existence of two or more distinct types of benzodiazepine receptors, in contrast to earlier results suggesting the presence of only one class of receptors. Appropriate thermoinactivation experiments indicate two receptors with different thermostabilities. Several triazolopyridazines, with some of the pharmacological properties of anxiolytics have recently been shown to displace 3H-diazepam and 3H-flunitrazepam with Ki values in the 6 to 100 nanomolar range. These new substances are active in conflict tests in rats and monkeys and prevent metrazol induced seizures in vivo, but strikingly lack the ataxia and sedative properties of the benzodiazepines. Hill analyses of dose-response curves for some of these substances yields Hill coefficients in the range of 0.4--0.6, suggesting that these compounds may be able to discriminate between several types of benzodiazepine receptors.
398 citations
TL;DR: It is proposed that two biochemically distinct BDZ receptors exist in brain which are responsible for the mediation of different pharmacological activities.
Abstract: Brain-specific binding sites have been isolated on synaptosomal membrane fragments which recognize pharmacologically active benzodiazepine (BDZ's) and triazolopyridazines (TPZ's). While early evidence indicated the existence of a single homogeneous class of BDZ binding sites, more recent biological and pharmacological studies support the notion of BDZ receptor multiplicity. We now propose that two biochemically distinct BDZ receptors exist in brain which are responsible for the mediation of different pharmacological activities. Type I BDZ receptors display a high affinity for both BDZ's and TPZ's, are not coupled to GABA receptors or to chloride ionophores, and are the sites which mediate anxiolytic actions. Type II BDZ receptors display a high affinity for BDZ's display a low affinity for TPZ's, are coupled to GABA receptors and/or chloride ionophores, and are the sites which mediate pharmacological effects other than anxiolytic activity.
396 citations
TL;DR: CL 218,872 is the first non-benzodiazepine to selectively displace brain specific 3H-diazepam binding with a potency comparable to that of the benzodiazepines.
Abstract: CL 218,872 is the first non-benzodiazepine to selectively displace brain specific 3H-diazepam binding with a potency comparable to that of the benzodiazepines. Like the benzodiazepines, CL 218,872 increased punished responding in a conflict situation and protected against the convulsions induced by pentylenetetrazole. These three pharmacological properties are highly predictive of anxiolytic activity. Unlike the benzodiazepines, however, CL 218,872 was relatively inactive in tests designed to measure effects on neuronal systems which utilize GABA, glycine and serotonin as transmitters. Furthermore, CL 218,872 was relatively free of the ataxic and depressant side effects commonly associated with the benzodiazepines. Because of this high degree of selectivity, CL 218,872 may represent a new probe for investigating neuronal substrates of anxiety.
277 citations
TL;DR: Naloxone appears to markedly reduce appetitive behavior, particularly water intake, following deprivation in both rats and mice, and the fact that low doses of nalox one can elicit these effects suggests that the drug is acting at specific tissue sites, possibly endorphine recpetors.
Abstract: Naloxone, an opiate antagonist, was administered to male and female rats and male mice after periods of food or water deprivation ranging from 12 to 48 hr. Naloxone (0.01–10 mg/kg) reduced postdeprivational water intake in most groups of rats and mice in a dose-related manner. Naloxone suppression of water consumption appeared to be independent of sexual differences in rats, and phase of the diurnal cycle, and length of the deprivation interval in both rats and mice. Postdeprivational food intake in male rats and mice was also reduced by naloxone in a dose-dependent fashion. This naloxone effect was less pronounced than actions observed with water intake, and tended to diminish with lengthening food deprivation periods. In general, mice appeared to be less sensitive than rats to naloxone suppression of food and water intake. Naloxone appears to markedly reduce appetitive behavior, particularly water intake, following deprivation in both rats and mice. The fact that low doses of naloxone can elicit these effects suggests that the drug is acting at specific tissue sites, possibly endorphin receptors.
275 citations
TL;DR: There is lateralisation of function in the chicken fore-brain by examining the behavioural modifications produced by administration of cycloheximide into the left or right hemisphere on Day 2 of post-hatched life.
Abstract: There is lateralisation of function in the chicken fore-brain This was revealed by examining the behavioral modifications produced by administration of cycloheximide into the left or right hemisphere on Day 2 of post-hatched life Visual discrimination learning of a task requiring a search for food was found to be performed either entirely or, at least, to a greater extent by the left hemisphere Visual habituation learning was not found to be lateralised The left hemisphere is more involved in auditory habituation than is the right; administration of cycloheximide to the left hemisphere slowed auditory habituation, as did bilateral administration, but treatment of the right hemisphere was ineffective There are indications that the right hemisphere plays a more important role in response to novelty A side-preference for response to stimuli seen by the left eye was demonstrated These results are discussed with reference to head orientation during development in the egg
228 citations
TL;DR: Increases of pulse rate, facial skin temperature and carotid arterial pressure and blood flow rate, as well as changes of digital plethysmogram and electrocardiogram, and elevation of blood acetaldehyde did not occur in the non-flushing group, but urinary excretions of epinephrine and norepinephrine increased in the flushing cases after the drinking.
Abstract: Normal subjects were divided into two groups, i.e., those showing, and those not showing, facial flushing after consuming a small amount of alcohol. In the flushing group, increases of pulse rate, facial skin temperature and carotid arterial pressure and blood flow rate, as well as changes of digital plethysmogram and electrocardiogram, were found together with a conspicuous rise in blood acetaldehyde levels after the drinking. However, significant changes of the signs as mentioned above and elevation of blood acetaldehyde did not occur in the non-flushing group. The maximum blood alcohol levels and the rate of alcohol elimination showed not difference between these two groups. Furthermore, urinary excretions of epinephrine and norepinephrine increased in the flushing cases after the drinking.
216 citations
TL;DR: The results indicate that pimozide reduces self-stimulation by abolishing the rewarding effect of brain stimulation rather than by interfering with motor ability.
Abstract: Rats stopped responding for electrical stimulation of the brain following pretreatment with the dopamine antagonist pimozide, as well as following truncation of brain stimulation trains. In either case the extinguished responding was temporarily reinstated on presentation of a light if the light had previously signalled reward but not if the light had had no such significance. These results indicate that pimozide reduces self-stimulation by abolishing the rewarding effect of brain stimulation rather than by interfering with motor ability.
185 citations
TL;DR: The effects of minor tranquilisers and of stimulant drugs were studied in the Social Interaction test of anxiety: whereas phenobarbitone increased social interaction regardless of the test illuminance and unfamiliarity, the increase produced by flurazepam was limited to the more stressful test conditions.
Abstract: The effects of minor tranquilisers and of stimulant drugs were studied in the Social Interaction test of anxiety in which the illuminance and unfamiliarity of the test arena are manipulated. Acute administration of sodium phenobarbitone (25 mg/kg) was without effect. Acute administration of sodium phenobarbitone (35 mg/kg) and of meprobamate (60 mg/kg) produced sedation: both locomotor activity and social interaction were reduced. On the other hand, amphetamine sulphate (2 mg/kg) and caffeine citrate (20 mg/kg) reduced social interaction, but increased locomotor activity. Chronic administration dissociated the pattern of results produced by sodium phenobarbitone (35 mg/kg) from that produced by flurazepam (0.5 mg/kg). With chronic treatment (5 days) neither drug reduced motor activity, but whereas phenobarbitone increased social interaction regardless of the test illuminance and unfamiliarity, the increase produced by flurazepam was limited to the more stressful test conditions, i.e., when the arena was unfamiliar or brightly lit.
184 citations
TL;DR: Data indicate that the effects of neuroleptics on operant behavior cannot be accounted for in terms of unitary actions such as specific motor impairments or blockade of primary reinforcement, rather these drugs appear to have multiple behavioral effects.
Abstract: Previous experiments have noted that the reduction in operant behavior following treatment with neuroleptic drugs resembles an extinction curve. From this it has been argued that neuroleptic drugs disrupt operant responding by blocking the hedonic properties of primary reinforcers. The present series of experiments challenge this interpretation on several grounds. Rats were trained to bar-press either for food or for brain-stimulation reward on a variable interval (VI-60 sec) schedule. They were subsequently put into a condition of non-reward (i.e. extinction) and the effects of haloperidol (0.1 mg/kg) on the rate of responding during extinction were examined. According to the anhedonia hypothesis haloperidol should not further reduce responding during extinction. Contrary to the prediction it was found that the rate of responding during haloperidol and extinction was greatly reduced compared to that measured during extinction alone. Furthermore, the anhedonia hypothesis has maintained that following neuroleptic treatment, response patterns change only after the animal has been reinforced on several occasions. However, in the third experiment of the present study which employed a VI-4 min schedule of food reinforcement, the response rate often was attenuated prior to the first reinforcement. These data indicate that the effects of neuroleptics on operant behavior cannot be accounted for in terms of unitary actions such as specific motor impairments or blockade of primary reinforcement. Rather these drugs appear to have multiple behavioral effects.
160 citations
TL;DR: Biochemical, electrophysiological and behavioral experiments highlight the possible importance of frontal cortex in mediating the anxiolytic properties of the benzodiazepines and provide insights into the nature of the endogenous ligand.
Abstract: Brain specific benzodiazepine receptors appear to mediate the pharmacological properties of benzodiazepines. A neuronal localization for these receptors is suggested by the parallel decrease in the number of benzodiazepine receptors and cerebellar Purkinje cells in “nervous” mutant mice. Electrophysiological results are compatible with an action of benzodiazepines on neuronally localized, physiological receptors. Biochemical, electrophysiological and behavioral experiments highlight the possible importance of frontal cortex in mediating the anxiolytic properties of the benzodiazepines. Triazolopyridazines act upon benzodiazepine receptors, increase punished responding and protect against pentylenetetrazole-induced convulsions, but do not produce the side effects associated with benzodiazepines or affect classical neurotransmitter systems. The structural similarities between triazolopyridazines, purines and the indole portion of certain peptides may provide insights into the nature of the endogenous ligand.
TL;DR: It is suggested that stimulus generalization with cocaine may be contingent upon increasing the functional availability of endogenous dopamine and, perhaps, of norepinephrine irrespective of the presynaptic mechanism from which such increase may result and that differential stimulus generalized of drugs with cocaine (in terms of dose, subjects, slope, and rate effects) may parallel their differential primary reinforcing properties.
Abstract: The experiments reported here were undertaken to examine the neuropharmacological characteristics of drugs inducing stimulus generalization with cocaine as a cue. Experiment 1 indicated that d-amphetamine (ED50: 0.17 mg/kg), 1-amphetamine (0.45 mg/kg), methylamphetamine (0.15 mg/kg), methylphenidate (0.55 mg/kg) and nomifensine (0.32 mg/kg) induce stimulus generalization with cocaine in rats trained to discriminate 10 mg/kg cocaine from saline; this generalization occurred in 100% of the animals, proceeded along steep slopes (s: 1.27 to 1.88 in log-probit plots), and was not associated with behaviorally toxic effects. Amantadine (57.8 mg/kg; s=1.85), apomorphine (0.33 mg/kg; s=1.77), piribedil (8.4 mg/kg; s=10.6) and bromocryptine (>40 mg/kg) also induced stimulus generalization to some extent, but this generalization was partial in some cases, proceeded along a shallow slope with piribedil, and was invariably associated with severe rate depressant effects. Ten mg/kg, but not 1.25 mg/kg hydroxyamphetamine induced generalization in 3 out of 8 rats. Experiment 2 revealed that tranylcrypromine (2.5 mg/kg; s=1.7), fentanyl (0.068 mg/kg; s=1.34), morphine (>10 mg/kg), phencyclidine (0.81 mg/kg; s=1.43), and benztropine (9.2 mg/kg) induce stimulus generalization with cocaine, whereas lidocaine, procaine, chlordiazepoxide, imipramine, desipramine, mescaline, LSD, isopropamide, and atropine do not. Experiment 3 shows that propranolol (1.25 to 40 mg/kg) and isoproterenol (0.63 to 2.5 mg/kg) induce a biphasic generalization with cocaine. Experiment 4 discloses that rats trained to discriminate 10 mg/kg propranolol from saline generalize their training drug along a linear gradient, but generalize cocaine along a biphasic gradient. It is suggested (a) that stimulus generalization with cocaine may be contingent upon increasing the functional availability of endogenous dopamine and, perhaps, of norepinephrine irrespective of the presynaptic mechanism from which such increase may result and (b) that differential stimulus generalization of drugs with cocaine (in terms of dose, subjects, slope, and rate effects) may parallel their differential primary reinforcing properties.
TL;DR: There was a significant tendency for the within-group variabitliy to increase as the level of prenatal exposure increased, perhaps indicating that the incidence as well as the severity of behavioral dysfunction was dose dependent.
Abstract: Pregnant female rats consumed liquid diets containing either 35, 17, or 0% of the total calories as ethanol. Offspring of these females were tested for spontaneous alternation at 21 days of age and for several learning in a T-maze shock-escape paradigm at 20–21 days of age. In the spontaneous alternation test, rats exposed to alcohol prenatally took more trials than controls to enter the goal compartment opposite to that initially entered. In the T-maze escape study, alcohol-exposed offspring made more mistakes prior to criterion and more mistakes per trial than controls when the previously incorrect goal was made safe during reversal learning. In both studies linear dose-response functions were found. Furthermore, there was a significant tendency for the within-group variability to increase as the level of prenatal exposure increased, perhaps indicating that the incidence as well as the severity of behavioral dysfunction was dose dependent. The results are intepreted in terms of a delay in the development of a central inhibitory system.
TL;DR: The intracerebral microinjection technique was used to localize sites in the brain where morphine facilitated the self-stimulation rate at hypothalamic electrode sites and a possible dopaminergic substrate for the opiate induced behavioral stimulation is discussed.
Abstract: The intracerebral microinjection technique was used to localize sites in the brain where morphine facilitated the self-stimulation rate at hypothalamic electrode sites. Bilateral injections of morphine (2 x 1 microgram) into the ventral tegmental area and substantia nigra produced the strongest enhancement at the shortest latencies. At these sites, bilateral injections of 200 ng of morphine also produced a significant enhancement whereas a dose of 50 ng was below threshold for the rate increasing effect. The enhancement by morphine was effectively antagonized by naloxone (5 mg/kg). When injected bilaterally into the same area, D-Ala2-Met5-enkephalinamide (2 x 1 microgram) also induced a strong enhancement of self-stimulation lasting for 70 minutes. A possible dopaminergic substrate for the opiate induced behavioral stimulation is discussed.
TL;DR: The results suggest the possibility that MIF-I may represent a class of naturally occurring opiate antagonists with varying activities in independent situations.
Abstract: The effects of MIF-I (Pro-Leu-Gly-NH2) were examined in three experimental conditions in which the opiate antagonist naloxone is active. MIF-I was found to block the analgesic effects of enkephalins and also morphine in the tail-flick test but not in the vas deferens assay. Unlike naloxone, MIF-I did not seem to reduce food intake in VMH-lesioned rats. The results suggest the possibility that MIF-I may represent a class of naturally occurring opiate antagonists with varying activities in independent situations.
TL;DR: Physostigmine and methamphetamine alleviated most of the memory deficits and sedation produced by scopolamine and produced subjective arousal and a small improvement in recall of words learned after injection and a large increase in incorrect responding.
Abstract: Seventy college age subjects learned and recalled a series of word lists prior to being injected with methamphetamine (0.2 mg/kg or 0.3 mg/kg), scopolamine (8 microgram/kg), or a placebo. Following the injection subjects were tested for their free recall and recognition of the words and they completed a short-term digit recall task. Subjects who had previously received scopolamine were next injected with either methamphetamine (0.2 mg/kg or 0.3 mg/kg), physostigmine (32 microgram/kg), or placebo, while other subjects received a placebo injection. The above memory procedure was then repeated with a second series of word lists. In addition, subjective feelings were measured with a questionnaire. Scopolamine and methamphetamine did not affect recall of information learned prior to injection. Scopolamine did, however, impair performance in both the digit recall task and in the second series of memory tests. Physostigmine and methamphetamine alleviated most of the memory deficits and sedation produced by scopolamine. Methamphetamine alone produced subjective arousal and a small improvement in recall of words learned after injection and a large increase in incorrect responding.
TL;DR: Both male and female offspring prenatally exposed to ethanol weighed less than controls andFemale offspring performed significantly worse than the offspring of vehicle-injected pair-fed control mothers, on a two-way shock-avoidance task.
Abstract: In an initial study, the rate of blood alcohol disappearance was not significantly different in pregnant compared to nonpregnant rats, but blood alcohol levels were significantly different depending on dose. In a second study, pregnant rats received daily administrations (p.o.) of ethanol (30% w/v) in single doses throughout gestation. Pair-fed vehicle-treated, and nondrug-treated rats fed ad lib served as controls. All pups were removed from their biological mothers at birth and were raised by nondrug-treated surrogate mothers. At five months of age, both male and female offspring prenatally exposed to ethanol weighed less than controls and female offspring performed significantly worse than the offspring of vehicle-injected pair-fed control mothers, on a two-way shock-avoidance task. There were no significant group differences, however, for either sex in water-escape maze learning.
TL;DR: The minimal effect of naloxone and naltrexone on normal body temperature and on pyrogen-induced fever indicates that endogenous opioid peptides are unlikely to act physiologically via stimulation of receptors specifically sensitive to morphine, however, methionine-enkephalin is less readily antagonized by nalOXone and could have a physiologic role in thermoregulation through stimulation of another type of opiate receptor.
Abstract: Of the effects of morphine and endogenous opioid peptides on thermoregulation, the one which is most likely to be of physiologic significance is hyperthermia. This increase in body temperature is the result of coordinated changes in both physiological and behavioral thermoregulatory activities and, like fever, reflects an increase in the level about which body temperature is regulated. Morphine, endogenous opioid peptides and other opioids such as pentazocine all cause hyperthermia, but the considerable variation in the dose of naloxone required to antagonize the different agonists indicates that more than one type of opiate receptor is involved in these pharmacologic responses. The minimal effect of naloxone and naltrexone on normal body temperature and on pyrogen-induced fever indicates that endogenous opioid peptides are unlikely to act physiologically via stimulation of receptors specifically sensitive to morphine. However, methionine-enkephalin is less readily antagonized by naloxone and could have a physiologic role in thermoregulation through stimulation of another type of opiate receptor.
TL;DR: Behavioral analgesia and tolerance reported here may involve habituation to novel distractive stimuli associated with the hot plate test environment.
Abstract: Rats not exposed to a hot plate with or without morphine and later tested on the functional hot plate with or without morphine, displayed increased paw lick latency relative to same-injected rats given pretest hot plate exposure. This analgesic effect, was termed behavioral analgesia since it, unlike morphine-induced analgesia, was not reversed by naloxone (Experiment 2). Behavioral tolerance was evident in animals exposed to the nonfunctional hot plate regardless of drug treatment and was dissociated from pharmacological tolerance. Behavioral analgesia and tolerance reported here may involve habituation to novel distractive stimuli associated with the hot plate test environment.
TL;DR: The concept that stressful events induce analgesia through specific activation of an intrinsic pain-inhibitory system which has both opiate and non-opiate branches is supported.
Abstract: Acute exposure to severe stressors induce profound analgesia Repeated exposures to the same stressors esult in adaptation in much the same way that repeated administration of opiates results in tolerance The present study investigated whether two qualitatively different stressors, cold-water swims (CWS) and injections of 2-deoxy-D-glucose (2-DG) share common pain-inhibitory mechanisms by determining whether cross-tolerance developed to their analgesic effects Cross-tolerance was also examined between 2-DG and morphine Flinch-jump thresholds were determined in six groups of six rats each Analgesia was observed 30 min following acute exposure to CWS (2°C for 35 min), 2-DG (350 mg/kg) and morphine (10 mg/kg), but not following placebo injections or warm water swims Chronic exposure to all three analgesic treatments resulted in tolerance and adaptation Complete and reciprocal cross-tolerance developed between the analgesia induced by CWS and by DG Complete cross-tolerance to 2-DG analgesia also developed in morphine-tolerant rats, but only partial cross-tolerance to morphine analgesia developed in 2-DG adapted rats These results support the concept that stressful events induce analgesia through specific activation of an intrinsic pain-inhibitory system which has both opiate and non-opiate branches
TL;DR: Adult male Sprague-Dawley rats were placed in an apparatus consisting of 2 distinctive interconnected chambers and choice preferences developed and stabilized over three 30 min exposures to classical conditioning of opiate effects to distinctive environments.
Abstract: Adult male Sprague-Dawley rats were placed in an apparatus consisting of 2 distinctive interconnected chambers. Choice preferences developed and stabilized over three 30 min exposures. Central injection of morphine or an enkephalin analogue in conjunction with placement upon the nonpreferred side caused a preference shift which was not evident in control subjects. Classical conditioning of opiate effects to distinctive environments may offer a novel means of assessing the hedonic effects of these compounds.
TL;DR: It is concluded that opiate receptors located in the ventromedial hypothalamus are not essential for the effects of opiate agonists and antagonists on feeding behavior.
Abstract: Intraperitoneal injections of naloxone hydrochloride (1, 2, 4, and 8 mg/kg) suppressed food intake in both normal and hypothalamic obese rats maintained on a 4-hr per day feeding schedule. The decrease in feeding was more pronounced in the animals with ventromedial hypothalamic lesions. Appetitively motivated feeding, i.e., the consumption of sweetened milk under nondeprived conditions, was also suppressed by naloxone, but there was no reliable difference between groups. It is concluded that opiate receptors located in the ventromedial hypothalamus are not essential for the effects of opiate agonists and antagonists on feeding behavior.
TL;DR: Results are consistent with the theoretical proposition that a brain neurochemical change which might lead to social attraction is the activation of endogenous opioid systems when opiate activity is exogenously sustained.
Abstract: The effect of low (1 mg/kg) doses of morphine on maintenance of physical proximity were evaluated in paired rats observed in a 4 square foot test arena. Morphine reliably reduced proximity maintenance time, and this was apparently not due to sedation, since the effect was unmodified by doses of amphetamine which substantially increased motor activity. The effects of naloxone were inconsistent on this measure of social motivation. In general, the results are consistent with the theoretical proposition that a brain neurochemical change which might lead to social attraction is the activation of endogenous opioid systems. When opiate activity is exogenously sustained, animals exhibit a subnormal tendency to be gregarious.
TL;DR: It was found that orally ingested aluminum is absorbed by rats and deposited in the brain, and high brain aluminum levels are associated with rapid general activity, decreased ability to maintain roto-rod activity, and increased sensitivity to flicker.
Abstract: Abnormally high brain aluminum concentrations have been detected in hemodialysis patients who died of an unexplained encephalopathy. As a result, this study was undertaken to examine whether the ingestion of aluminum produces behavioral aberrations in non-dialysed human subjects and rats with ostensibly normal renal function. Rats were fed AlCl3 by intubation in varying doses, and tests measuring learning ability, visual temporal acuity, motor coordination and activity were administered. It was found that orally ingested aluminum is absorbed by rats and deposited in the brain. High brain aluminum levels are associated with rapid general activity, decreased ability to maintain roto-rod activity, and increased sensitivity to flicker. Behavioral tests were also given to elderly human subjects and performance correlated with serum aluminum level. High serum levels of aluminum in elderly humans are associated with impaired visuo-motor coordination, poor long-term memory, and increased sensitivity to flicker.
TL;DR: It is suggested that rats without previous history of drug dependence self-administer low doses of delta 9-THC and that the interaction between the food deprivation state and the environmental contingencies introduced by a FT-1 min schedule is a critical variable in the acquisition period.
Abstract: The present study examines the dose-response pattern of delta 9-tetrahydrocannabinol self-injection in naive rats at 80% reduced body weight and 100% body weight, both conditions with a fixed-time 1 min (FT-1) food delivery schedule. The results indicated that food deprived animals tested on a FT-1 min schedule self-injected low doses of delta 9-THC at a higher rate than those animals at 100% body weight and on a FT-1 min schedule. Animals at 80% reduced body weight without a schedule did not differ from rats self-injecting delta 9-THC at free feeding situation. These findings suggest that rats without previous history of drug dependence self-administer low doses of delta 9-THC and that the interaction between the food deprivation state and the environmental contingencies introduced by a FT-1 min schedule is a critical variable in the acquisition period.
TL;DR: The reversal learning capacity of young rhesus monkeys in visual discrimination tasks was examined during daily exposure to dietary lead acetate throughout the first year of life, and all lead-treated monkeys showed performance deficits on reversal learning tasks.
Abstract: The reversal learning capacity of young rhesus monkeys in visual discrimination tasks was examined during daily exposure to dietary lead acetate throughout the first year of life. While not affected in physical development, all lead-treated monkeys showed performance deficits on reversal learning tasks. These deficits were independent of lead-induced changes in motivation. Over a series of problems, the overall learning rate of monkeys with blood lead concentrations in the range of 70–90 μg/dl was retarted, which resulted partly from a pronounced difficulty in attaining criterion on the first of a series of reversals within a given problem. This latter deficit resulted from an increase in errors, balks, and total trials to criterion on the first reversal. Monkeys exposed to blood lead concentrations of 40–60 μg/dl required significantly more trials to finish all problems, but did not show the first-reversal deficit. Theoretical implications of these data were discussed.
TL;DR: It was suggested that shock may differentially affect motivation or arousal in rehabilitated and control animals.
Abstract: A period of severe early iron deficiency (birth to 28 days of age) produced a persistent deficit (22%) in brain non-heme iron in adult rehabilitated animals. Long-term effects on behavior and physiological responsiveness were also observed. Although rehabilitated and control animals did not differ either in basal levels of plasma corticosterone or in the time course of the stress response following ether and cardiac puncture, possible differences in pituitary-adrenal responsiveness appeared to emerge following testing in an exploratory task. In addition, significant differences between rehabilitated and control animals were observed in both active and passive avoidance learning. Rehabilitated males made more intertrial responses than control males during active avoidance learning, and rehabilitated animals of both sexes performed better (i.e. showed longer reentry latencies) in a passive avoidance situation. It was suggested that shock may differentially affect motivation or arousal in rehabilitated and control animals.
TL;DR: A conditioned taste aversion paradigm was employed to examine the ontogenetic trend in psychopharmacological responsiveness to amphetamine among infant, periadolescent, and young adult rats to parallels the previously examined ontogenetics trend in amphetamine response using locomotor activity as a response measure.
Abstract: In this study a conditioned taste aversion paradigm was employed to examine the ontogenetic trend in psychopharmacological responsiveness to amphetamine among infant (18 days of age), periadolescent (35 days of age), and young adult (52 days of age) rats. The ability of amphetamine to alter taste preference increased with dosage level and this effect interacted with age. Infant rats demonstrated greater sensitivity to the taste aversion inducing properties of amphetamine than either periadolescent or young adult animals. In contrast, periadolescent animals demonstrated a marked resistance to amphetamine's taste aversion inducing properties when compared with either infant or young adult animals. This developmental pattern in amphetamine drug responsiveness seen utilizing the taste aversion paradigm parallels the previously examined ontogenetic trend in amphetamine response using locomotor activity as a response measure.
TL;DR: There was a parallel between analgesia tolerance and some, but not all, signs of physical dependence in rats treated with daily intraperitoneal injections of morphine sulfate.
Abstract: The influence of treatment dose on a number of characteristics of opiate tolerance was studied in male Sprague-Dawley rats treated with daily intraperitoneal (IP) injections of morphine sulfate. Zero, 7.5, 15, 25 or 45 mg/kg/day was given for 34 consecutive days and the degree of morphine effect on four different tests was periodically assessed. Dose-related effects on tailflick latency (tail immersion test, 1.5 hr post injection), swimming test (2 hr post injection), and body weight gain revealed the development of tolerance; there was a non-dose-related hyperthermia (1.5 hr post injection) to which rapid sensitization occurred. All changes reached asymptote and the rate and extent of change varied with the test. Plots of log response vs test day for tailflick and swimming indicated an early steep component and a later less steep component of decline. Subsequent testing indicated that the log-dose/response (LDR) curves for tailflick latency and time to maximum hyperthermia shifted to the right by an amount dependent on the treatment dose; there was no change in the curve for hyperthermia duration. In high dose groups no further shift occurred, but the tailflick LDR curves became flattened. The tailflick LDR curve changes were replicated in rats treated for 24 days with 0, 8, 24, 48, 96, or 240 mg/kg/day. Subsequently, a constellation of withdrawal signs precipitated by naloxone HCl (1 mg/kg, IP) was measured. On the basis of the relation between treatment dose and the magnitude of the various measures, there was a parallel between analgesia tolerance and some, but not all, signs of physical dependence.
TL;DR: The results indicate that a small amount of essentially intact peptide can cross the blood-brain barrier and could represent one of the mechanisms by which central effects of peripherally injected peptides can be exerted.
Abstract: It was determined that an antiserum against delta-sleep inducing peptide (DSIP) required eight of the nine constituent amino acids for antigenic activity. Measurement by this radioimmunoassay (RIA) of DSIP-like material in the rat brain, therefore, would necessarily involve almost the entire molecule present in essentially intact form. Injection of 200 μg DSIP into the carotid artery of rats resulted in a doubling of brain levels of peptide as measured shortly afterwards by RIA. The brain tissue to plasma ratio of radioactivity in rats injected with labeled DSIP was much higher than that in rats injected with labeled inulin; this suggests that the increased amount of material measured by RIA was not merely trapped in the blood vessels. Thus, the results indicate that a small amount of essentially intact peptide can cross the blood-brain barrier. This could represent one of the mechanisms by which central effects of peripherally injected peptides can be exerted.