Showing papers in "Pharmacology, Biochemistry and Behavior in 1980"

Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines

Abstract: A simple system is described to analyze the possibility that increased exploratory behavior is an index for the anxiolytic effects of benzodiazepines in laboratory rodents. Mice were allowed free run in a two-chambered arena, where two-thirds of the area was illuminated and one-third was darkened. The two chambers were separated by a black partition equipped with photocells across the opening, and the entire cage rested on an Animex activity monitor. Transitions across the partition between the light and dark chambers, and total Animex locomotor activity, were increased by clonazepam and chlordiazepoxide, in dose-dependent ranges consistent with previously reported behavior models. The increased exploratory activity with benzodiazepines does not appear to be a non-specific increase in general motor activity, as locomotion in clonazepam and chlordiazepoxide treated mice placed in a bare, undifferentiated cage was not significantly different from vehicle treated mice.

Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens.

Abstract: The effect of 6-OHDA injections into the nucleus accumbens was examined on cocaine self-administration behaviour. Rats were given access to cocaine (0.75 mg/kg/inj.) for three hours/day on a continuous reinforcement schedule. After daily intake of cocaine had stabilized, rats were injected with 6-OHDA (8 μg/2 μl). When tested the day following the 6-OHDA injection most rats failed to self-administer cocaine, however this disruption did not resemble extinction. After several days self-administration recovered in many animals to near preoperative levels, and the rate of this recovery correlated (r = +0.75) with the levels of dopamine remaining in the nucleus accumbens. The animals with the greatest depletion of dopamine did not recover cocaine intake. In a separate experiment, animals were pretreated with desmethylimipramine and/or pargyline to achieve a more extensive and selective lesion. When tested five days after the lesion all animals in these 6-OHDA groups showed a significant decline in cocaine intake compared to vehicle injected control animals. Several 6-OHDA treated animals displayed a pattern of behaviour resembling extinction, where a high rate of lever pressing was followed by cessation of responding. Some animals were aalso tested for apomorphine self-administration and this was found not to be affected by the 6-OHDA treatment. These data support the hypothesis that non-striatal dopamine may subserve cocaine reward.

A rapid method for the regional dissection of the rat brain

Abstract: A method is described for the rapid dissection of seventeen areas of the rat brain. Regions from fresh unfrozen brain tissue are dissected from coronal brain slices obtained with use of a cutting block. This method is applicable to pharmacological and behavioral studies which require the dissection of numerous brains during short time intervals.

Reinforcing Effects of Morphine Microinjection into the Ventral Tegmental Area

Abstract: A neural substrate for the reinforcing property of an opiate drug was identified in the ventral tegmental area (VTA) by establishing conditioned reinforcement to salient environmental stimuli paired with intracerebral microinjections of morphine. Bilateral microinjections of morphine into the VTA in doses of 0.2 microgram and 1.0 microgram produced a subsequent change in place preference to a distinctive compartment previously associated with the stimulant effects of morphine. Microinjection of 1.0 microgram morphine at sites 2.5 mm dorsal to the VTA had no effect. Pretreatment with naloxone (2 mg/kg) antagonized the reinforcing effects of 1.0 microgram morphine as this group showed no significant change in place preference. Nor did control groups receiving microinjections of sterile physiological saline. Taken together, these data suggest that opiate receptors, located in the ventral tegmental area, play an important role in mediating the reinforcing effects of morphine. The possible involvement of dopaminergic neurons in these effects is discussed.

Action of drugs of abuse on brain reward systems.

Abstract: The finding that animals will work for electrical stimulation of some but not all parts of the brain has prompted the view that there are specialized brain circuits which subserve reward function. Two synaptic links in this circuitry have been partially identified. Studies of the effective stimulation parameters indicate that the directly activated fibers are usually high-frequency-sensitive, fast-conducting, myelinated fibers. Pharmacological studies suggest that all reward sites tested are afferent to a critical dopaminergic synapse; the myelinated, reward-relevant fiber of the medial forebrain bundle may synapse directly on the dopamine link. Dopamine blockers block self-stimulation regardless of electrode placement, and dopamine agonists are rewarding in their own right; thus the critical dopaminergic synapse plays both a necessary and (with its normal efferents) a sufficient role in reward function. Several drugs of abuse can facilitate self-stimulation, and it is hypothesized that they do so by a direct action on the same neural substrate. Amphetamine and cocaine seem to act directly in the critical dopamine synapse. Opiates might act at the dopamine synapse or cell bodies, or might act on dopamine afferents. Ethanol, barbiturates and benzodiazepines have not been extensively explored, but if their reported facilitations of self-stimulation are reliable they might be suggested to cause them by a naloxone-reversible inhibition of noradrenergic function, which disinhibits rather than directly excites the dopamine reward link. These suggestions as to the possible sites of interaction of drugs of abuse with brain stimulation reward circuitry are speculative, and are advanced as potentially heuristic working hypotheses.

Circling behavior in rats with partial, unilateral nigro-striatal lesions: effect of amphetamine, apomorphine, and DOPA.

Abstract: Partial, unilateral lesions of the nigro-striatal tract were produced in rats by injecting various quantities of 6-hydroxydopamine into the substantia nigra. The extent of each animal's lesion was estimated by comparing tyrosine hydroxylase activities in its lesioned and control striata. L-DOPA and apomorphine induced contralateral (i.e., away from the lesion) circling behavior only in rats in which more than 90% of the nigro-striatal system had been destroyed. In contrast, d-amphetamine caused turning in the ipsilateral direction when as few as 50% of the nigro-striatal neurons had been destroyed.

Effects of scopolamine, pentobarbital, and amphetamine on radial arm maze performance in the rat.

Abstract: Rats were trained to obtain food pellets from the end of each arm of an eight-arm radial maze. Baseline performance was characterized by very few entries into arms from which the food pellet had already been obtained. In Experiment 1, neither d-amphetamine (0.1-3.0 mg/kg) nor pentobarbital (1.0-10.0 mg/kg) affected choice accuracy, although the rate of arm-entry increased after d-amphetamine and decreased after pentobarbital. Scopolamine (0.1-1.0 mg/kg), on the other hand, reduced both accuracy and the rate of arm entry. In a second experiment, the effects of scopoalmine were replicated using a between-subjects design. Methylscopolamine (0.17, 1.0 mg/kg) was found to have little effect on performance. Multiple response criteria were also compared in the second experiment. Scopolamine was found to affect runs farther out the arm differently than it affected abbreviated arm entrances. A post-trial feeding test was also included to evaluate changes in reinforcer effectiveness, and showed that food continued to be a reinforcer after both scopolamine and methylscopolamine.

Two sensitive periods for the amnesic effect of anisomycin

Abstract: Impairment of retention of a brightness discrimination in rats was obtained when anisomycin (80 microgram bilaterally into both hippocampi) was injected 10 min before and 80 min after training or 240 and 360 min after training. No amnesia was observed when anisomycin was injected 45 and 165 min post training. The two separate sensitive periods for the amnesic effect of the inhibitor obviously correspond to the two phases of increased protein synthesis during the consolidation of the same learning procedure. The results support the previous findings of the two independent and qualitatively different macromolecular processes. They also argue for the inhibition of protein synthesis as an important mechanism in the amnesic effect of anisomycin.

Olfactory influences on the human menstrual cycle.

Abstract: Two groups of women were compared for the timing of the onset of their menstrual cycles. One group was rubbed on the upper lip (directly beneath the nose) with a mixture of alcohol and underarm perspiration collected from a single female donor. The other group was rubbed with plain alcohol. The group which received the perspiration showed a significant shift in the timing of their menstrual cycles which conformed closely with the donor's monthly cycle. This is a preliminary study which supports the hypothesis that the time of menstrual onset may be modified by olfactory cues.

The neurochemical control of crying

Abstract: The capacity of 18 drugs, including those which modify brain opioid, serotonin, norephinephrine, dopamine and acetylcholine activity, to modulate separation-induced distress vocalizations (DV) in young chicks were studied. Intraperitoneal morphine (1.7–5 mg/kg) injections were very effective in reducing DV's and naloxone (1.7–5.0 mg/kg) was found to increase DV's. Smaller bidirectional effects were also observed after pharmacological manipulation of cholinergic and serotonergic systems. Blockade of these systems with atropine (5–15 mg/kg) and methysergide (0.56 mg/kg) increased DV's while a facilitation of activity in these systems with pilocarpine (15 mg/kg) and quipazine (15 mg/kg) reduced DV's. Small reductions of DV's could also be achieved with neuroleptics such as haloperidol and chlorpromazine, and with apomorphine, suggesting that reduction of brain dopamine activity reduces DV's, while clonidine (0.56–1.7 mg/kg) was very powerful in reducing DV's, perhaps through autoreceptor reduction of brain NE activity. Chlordiazepoxide (5–15 mg/kg) was capable of reducing DV's, while imipramine (15–45 mg/kg), and pentobarbital (5–15 mg/kg) were essentially without effect. Opiate effects could be obtained as readily following intraventricular as following peripheral drug administration, while cholinergic and serotonergic agents were most effective by the peripheral route. In general, it was concluded that the opiate system had the most powerful specific effect on distress vocalization of all systems studied.

Pain modulating and reward systems: A single brain mechanism?

Abstract: The hypothesis that brain rewarding and pain modulating systems could involve a common opiate system, identically blocked by naloxone, has been tested in three experiments. The preferences or aversions for sapid solutions in rats have been employed as reliable measures of responses to rewarding or nociceptive stimulations. In the first experiment, it was shown that the spontaneous aversion to a quinine HCl solution was enhanced when rats were offered the solution 30 min after naloxone at a dose of 1 mg/kg. The same enhanced aversion was observed in the second experiment towards a sweet solution previously made aversive through a conditioned taste aversion paradigm. In the third experiment, by using two different procedures and saccharin or glucose solutions, it was found that naloxone acutely abolished the preference for sweet solutions versus water in rats. It is concluded that: (1) the enhancement by naloxone of the aversion to a sapid solution, similar to the naloxone induced hyperalgesia, allows to assimilate this aversion to other responses to nociceptive stimulations; (2) this suggests that, like other responses to nociceptive stimulations, this aversion is normally attenuated through the release of brain or pituitary opiates; (3) the suppressant effect of naloxone upon both this attenuation of aversion and a preference for a sapid solution supports the notion of a biochemical and functional community between rewarding and pain modulating systems.

Opioid blockade and social comfort in chicks.

Abstract: When young animals are separated from their normal social environment in groups they distress vocalize (DV) less than when isolated alone. Opioid blockade with naloxone (1 mg/kg peripherally, and 1 μg centrally) increased crying more in group tested chicks than individually tested ones. The serotonin receptor blocking agent methysergide and the cholinergic blocking agent atropine sulfate produced similar effects. The testing of birds in mirrored environments also produced a reduction of DV's, and all three receptor blocking agents augmented DV's more in mirrored environments than in mirrorless ones. However, in studies evaluating changes in this comfort response by facilitation of opiate, serotonin (5 HT), and acetylcholine (ACh) activity (with morphine, quipazine and pilocarpine, respectively), only morphine was found to magnify the comforting effect of mirrors. The effects of naloxone on contact comfort, and the acquisition and expression of imprinting were further evaluated, and opioid blockade reduced all these measures of social comfort. It is concluded, that endogenous opioid activity (and to a lesser extent, 5 HT and ACh) contribute to the comfort which animals derive from their social environment.

Effects of morphine, β-endorphin and naloxone on catecholamine levels and sexual behavior in the male rat

Abstract: Intraperitoneal administration of the opiate antagonist naloxone hydrochloride (30 mg/kg) to sexually experienced male rats caused a significant reduction in mount and intromission latencies, number of mounts preceding ejaculation and ejaculation latencies Intraperitoneal administration of naloxone (30 mg/kg) also stimulated persistant non-copulators to begin mating and to ejaculate within a twenty minute test period Conversely, intraperitoneal administration of morphine sulphate (6 mg/kg) as well as intraventricular injection of the endogenous opiate β-endorphin (6 μg) produced a complete loss of copulatory behavior in male rats The deficit in sexual behavior induced by β-endorphin was correlated with a significant increase in hypothalamic norepinephrine levels It is suggested that the endogenous opiates may be involved in the mediation of sexual behavior via an interaction with central catecholaminergic systems

Inappropriate use of albino animals as models in research

Abstract: Sensory-neural, biochemical-metabolic, and physiological anomalies occur in albino mammals. There are ontogenic and biochemical parallels between the senses, peripheral nervous system, endocrine glands, metabolism, and melanin pigmentation. All albino mammals examined have abnormal optic systems. Many drugs cannot be adequately evaluated in an albino model because of melanin's ability to bind and interact with some chemicals. There is evidence that a general reduction in melanin pigment is correlated with a paucity of amino acids necessary for normal chemical function of the brain. There is a high probability that enzyme levels indicative of metabolic performance are deficient in the liver and kidneys of albinos. Congenital defects are associated with hypopigmentation in animal models and human syndromes. Melanin is found in abundance in the eye, inner ear, and midbrain where neural impulses are initiated indicating a possible role as an electrophysiologic mechanism. Microwave irradiation differentially affects albino and pigmented animals. Implications of these observations and other reports of anomalies associated with hypopigmentation suggest caution in the use of albino and other hypomelanotic animals as normal models in biological research.

Characterisation of adjustments to the structure of feeding behaviour following pharmacological treatment: effects of amphetamine and fenfluramine and the antagonism produced by pimozide and methergoline.

Abstract: An observational procedure for examining the micro-structure of eating has been employed to establish the characteristic behaviour patterns displayed after various pharmacological manipulations. Using a double dissociation design it was shown that amphetamine and fenfluramine gave rise to quite distinctive readjustment to the structure of feeding behaviour. Amphetamine anorexia was characterized by a long initial delay, following which feeding was typified by infrequent short bursts of rapid eating. These effects were antagonised by the dopamine receptor blocking agent, pimozide. Fenfluramine exerted a more restricted pattern of action characterised by a marked slowing of the rate of eating. This effect was countered by the serotonin receptor blocking agent methergoline. These data throw light on the way in which pharmacological agents may impede food consumption and upon the neurochemical systems believed to be involved in the expression of feeding behaviour.

Increased self-administration of d-amphetamine after destruction of 5-hydroxytryptaminergic neurons.

Abstract: Rats will initiate self-administration of d-amphetamine and achieve a stable injection rate within 7-10 days. Animals injected intraventricularly with 5,7-dihydroxytryptamine, which selectively destroys 5-hydroxytryptamine-containing neurons, consistently self-injected larger amounts of d-amphetamine from the first day of training, but the acquisition of a stable rate of drug self-administration was not altered. Bilateral microinjection of 5,7-dihydroxytryptamine into nucleus accumbens failed to alter either the acquisition of d-amphetamine self-administration or the maintenance of a stable rate of injection.

Pimozide-induced suppression of responding: Evidence against a block of food reward

Abstract: Male albino rats injected with 0.5 or 1.0 mg/kg pimozide showed a decline in the rate of lever pressing on a continuously reinforced schedule for food reward. A similar decline was seen when responding was no longer reinforced (extinction). On this basis, Wise et al. [15] have previously hypothesized that pimozide blocks the reinforceing effects of the food pellets. However, in the present experiments the effects of pimozide were found to be additive with those of extinction so that animals treated with pimozide and placed into extinction ceased responding more quickly than animals subjected to either manipulation on its own. In addition, the effects of one condition failed to transfer to the other condition so that animals exposed to three days of pimozide failed to show a further decline when exposed to a day of extinction under vehicle and vice versa. Similar additivity and failure of transfer were seen on a DRL schedule for food reward; however, using this schedule pimozide failed to produce a decline in reinforced responding. In a further experiment pimozide failed to mimic extinction by blocking the reinforcing effects of food so as to cause a partial reinforcement extinction effect in a runway. It is concluded that these effects of pimozide on operant behavior are not mediated by block of reward.

Rewarding and aversive effects of morphine: Temporal and pharmacological properties ☆

Abstract: To assess morphine-induced location preferences and flavor aversions, rats were administered morphine sulfate (10 mg/kg, IP) either immediately before (Experiment 1) or immediately after (Experiment 2) confinement for 20 min in one side of a shuttlebox with access to a flavored solution. On control trials the rats were administered saline and confined for 20 min on the opposite side with a differently flavored solution. In subsequent choice tests, it was found that morphine injections before confinement produced a preference for the side associated with morphine and indifference to the flavors, whereas morphine injections after confinement produced an aversion to the flavor paired with morphine and indifference to the sides. Experiments 3 and 4, using a procedure similar to that of Experiment 1, showed that naloxone (1 mg/kg, IP) blocked the morphine-induced side preference, although given alone it was without effect in this test.

Elevated blood acetaldehyde in alcoholics with accelerated ethanol elimination

Abstract: Alcoholics and controls given ethanol (1.2 g/kg body weight) were analyzed for blood and breath acetaldehyde using the more sensitive and reliable semicarbazide method. The acetaldehyde levels in controls were almost undetectable (less than 2 microM), but were found to be elevated (10--10 microM) in 6 of 8 alcoholics. Breath acetaldehyde and blood acetaldehyde co-fluctuated during the experiments. Fructose infusion transiently increased blood acetaldehyde, but only in 4 of the alcoholics. The apparent discrepancy between our finding and the simultaneously reported low acetaldehyde level in alcoholics (Eriksson and Peachy, this volume) may be explained by the different status of the alcoholics tested. Our alcoholics were tested on the day after hospital admission and eliminated ethanol 5% faster than controls. It is suggested that elevated blood acetaldehyde occurs regularly after interrupted drinking in heavy alcohol abusers with fast ethanol elimination, possibly combined with reduced liver aldehyde dehydrogenase activity, but that the phenomenon may rapidly disappear upon abstinence and hospital treatment, which reduces disturbances in hepatic functions and the ethanol elimination rate.

Morphine selectively influences macronutrient intake in the rat.

Abstract: Dietary self-selection of the three macronutrients, protein, carbohydrate and fat, was examined in male rats following the administration of three doses of morphine sulphate: 10 mg, 15 mg, and 30 mg/kg body weight. Intakes of all three macronutrients were suppressed in a dose-dependent manner for a two-hour period following morphine administration. Both protein and carbohydrate intakes remained suppressed for a six-hour feeding period after morphine injections. In contrast, animals increased fat intake during the final four hours of the six-hour feeding period resulting in an overall increase in fat intake.

Effects of pimozide on lever pressing behavior maintained on an intermittent reinforcement schedule.

Abstract: Lever pressing for food on a variable interval (2.5 min) schedule was challenged by pretreatment with a 1.0 mg/kg dose of the dopamine receptor blocker pimozide. Large decreases in response rate were recorded even during the first few minutes of the test session before the rats had received any reinforcement. Pimozide also caused extinction-like effects, but it was clear, from comparisons between pimozide-treated rats that were rewarded and pimozide-treated rats that were not rewarded, that the rewarding effects of food were not totally blocked. It is suggested that an important aspect of the pimozide-produced response decrement is its effect on the incentive motivational properties of food-associated apparatus cues known to be important in sustaining responding under extinction and partial reinforcement conditions.

The excitatory component of ethanol in mice: a chronic study.

Abstract: The effects of chronic administration of initially depressant, ineffective and excitatory doses of ethanol on the locomotor activity of mice was studied. The results showed that (1) an excitatory effect of ethanol is observed after tolerance develops to its depressant action; (2) the effect induced by an initially excitatory dose of ethanol became more pronounced with chronic exposure to the drug; and (3) tolerance to the excitatory effect was not reached after 60 days of ethanol treatment.

Reduction of heroin intake in baboons by an economic constraint

Abstract: Baboons earned their total food ration in a situation where they were periodically given an opportunity to choose between food and an intravenous infusion of heroin. As the number of daily choices was restricted, food intake remained relatively constant, while heroin intake decreased dramatically.

Quantitative estimation of abnormal microheterogeneity of serum transferrin in alcoholics

Abstract: A qualitative abnormality of the microheterogeneity of serum transferrin, demonstrated by isoelectric focusing, has previously been shown to be a highly specific indication of chronic alcoholism. The abnormality consists of a selective increase of a cathodal transferrin component which is probably caused by a reduction of the sialic acid content. The present study describes a method for quantitative estimation of the abnormal transferrin. The technique was based on analytical isoelectric focusing as the first step followed by direct immunofixation. The immunofixed transferrin was quantified by computerized on-line densitometry, and the transferrin abnormality was calculated as a quotient, where the amount of the cathodal component was expressed as a percentage of the relative total immunofixed transferrin quantity. This method was shown to possess high sensitivity and good reproducibility. In the controls the mean value of the quotient was 3.7%, while in the alcoholics it was 9.5% which was a highly significant difference (p less than 0.001). The possible functional significance of a disturbed sialic acid metabolism in alcoholism is discussed.

Post-amphetamine depression of self-stimulation responding from the substantia nigra: Reversal by tricyclic antidepressants

Abstract: The effects of long-term amphetamine treatment were examined on self-stimulation responding from the substantia nigra. Rates of self-stimulation responding were substantially depressed among rats chronically treated with amphetamine and tested in the absence of the drug. When rats were subsequently retested after a two day hiatus in which they received imipramine or amitriptyline, the post-amphetamine depression of rates of self-stimulation responding was mitigated. The efficacy of imipramine and amitriptyline in reversing the post-amphetamine depression of self-stimulation responding was also evident during a continuation of the drug (imipramine or amitriptyline)/test sequence, for seven test sessions. The results of the present investigation were related to changes in dopamine and acetylcholine neurotransmission following long-term amphetamine treatement.

Cumulative dose-response curves in behavioral pharmacology.

Abstract: Cumulative dose-response curves have been widely used in many areas of pharmacology To date, the applicability of cumulative dose-response curves has not been assessed in behavioral pharmacology To determine the feasibility of this procedure, mice were trained to respond under a multiple time-out 5 min, fixed-ratio 30 (mult TO 5, FR 30) schedule of reinforcement The FR 30 component consisted of 15 presentations of an FR 30 schedule of reinforcement At the start of each TO 5 component, an intraperitoneal (IP) injection was given, and the effect on the response rate during the following 15 presentations of the FR 30 schedule was assessed d-Amphetamine (03--30 mu moles/kg), pentobarbital (3-300 mu moles/kg), morphine (1-100 mu moles/kg), ketamine (3-300 mu moles/kg), and phencyclidine (1-100 mu moles/kg) all produced dose-related decreases in FR responding In each case the lowest dose tested was without effect, and the highest dose tested essentially eliminated responding As a control, the normal 4th dose in the ascending series of each drug was given preceded by 3 saline injections Whether this dose of each drug was preceded by 3 separate saline injections or by 3 lower ascending doses of the same drug, the observed effect was identical Five consecutive saline injections during the experimental session were without effect The application of this procedure should greatly decrease the time required to examine the behavioral effects of a wide range of doses

Pre- and postsynaptic serotonergic manipulations in an animal model of depression☆

Abstract: Rats working on a food-reinforced operant schedule and exhibiting behavioral depression following administration of D,L-5-hydroxytryptophan (5-HTP) were pretreated with one of three drugs: methysergide, fluoxetine, or amitriptyline. The former two drugs were used to establish a basis for distinguishing between pre- and postsynaptic events. We found that methysergide, a known postsynaptic blocker of serotonin, almost completely abolished the depressive effect of 5-HTP, whereas fluoxetine, a known specific uptake blocker of serotonin, potentiated the depressive effect of the 5-hydroxytryptamine (5-HT) precursor. Amitriptyline, one of the commonly prescribed antidepressive drugs, reduced the behavioral depression following 5-HTP by approximately 50%. These data indicate that amitriptyline can act as an antagonist of 5-HT at the postsynaptic receptor. The results of this study, as well as those recently reported from CNS membrane binding studies, suggest that the therapeutic effects of some antidepressive drugs may be explained by their postsynaptic rather than presynaptic properties at central serotonergic receptors. Thus, these studies support the hypothesis that some types of human depression may be primarily due to an excess of free 5-HT acting at postsynaptic receptors.

Iron deficiency during early development in the rat: behavioral and physiological consequences.

Abstract: An iron deficient diet regimen from birth through 28 to 30 days of age produced animals with decreases levels of brain non-heme iron as well as decreased brain weight and hematocrit. Weight gain was also somewhat slower. In contrast, brain levels of cytochrome c were not reduced. During subsequent testing iron deficient animals were less responsive than controls in a mildly aversive novel situation (the open field), and ambulated less in an exploratory task (the hole-board). Iron deficient males also exhibited longer response latencies when first exposed to the passive avoidance platform, but following shock, iron deficient animals of both sexes exhibited longer reentry latencies. Measurement of plasma levels of corticosterone indicated that although iron deficient animals had elevated basal levels of corticoids, they exhibited a smaller stress increment than controls when exposed to the combined stress of ether and cardiac puncture. Data from the three behavioral tasks taken together with the pituitary-adrenal response to ether and cardiac puncture suggest that iron deficiency may reduce an animal's general responsiveness to environmental stimuli.

Behavioural and endocrine effects of naltrexone in male talapoin monkeys.

Abstract: The effect of treating captive male talapoin monkeys with naltrexone hydrochloride (500 μg/kg intra-muscular injection twice daily) was studied both in socially living and singly caged animals. The behaviour of the group males and endocrine changes in all treated animals were monitored during the course of treatment and on drug withdrawal. Naltrexone significantly reduced sexual behaviour in previously active males, while increasing grooming interactions. Aggressive behaviour did not change. There was an overall significant elevation in testosterone, LH and cortisol during drug treatment and a significant decrease on withdrawal. Changes in prolactin in response to naltrexone depended upon the pre-treatment level of this hormone; in males in which levels were low, there was a significant elevation in prolactin, while in those with high pre-treatment prolactin, levels were unchanged by the drug. The behavioural changes reported for this primate are in direct contrast to changes reported in rodents, while the hormonal changes, except for prolactin, are comparable to others reported.

Calcitonin reduces feeding in man, monkey and rat.

Abstract: It is proposed that calcitonin is a hormonal mediator of the satiety reflex. To test this hypothesis, effects of calcitonin on feeding and drinking were measured in rats and in rhesus monkeys. In monkeys, calcitonin produced severe (90%) and prolonged (3–5 days) reduction in feeding, and smaller decreases in drinking. In rats calcitonin decreased feeding in a dose-related manner over 24 hours, but increased drinking and urine output. A modest loss in body weight (2%) was also observed in psychiatric patients given calcitonin. It is suggested that calcitonin reduces feeding either through its effects on calcium metabolism, or by a direct action on the central nervous system.