Showing papers on "Opiate published in 1991"

Mechanisms of the analgesic actions of opiates and opioids.

Abstract: It is now clear that there are three sub-types of the opiate receptor, mu, delta and kappa. Evidence for differential roles of these sub-types in pain modulation is accumulating since the advent of relatively selective agonists and more recently, antagonists for the three receptors. The actions of opioids in the spinal cord is reasonably well understood and there is increasing knowledge of supraspinal sites of action, peripheral analgesic effects in inflammatory states and in the interactions between opioid and non-opioid systems at spinal levels, which may start to explain some of the clinical states with altered opioid sensitivity.

Testing Human Hair for Drugs of Abuse. III. Identification of Heroin and 6-Acetylmorphine as Indicators of Heroin Use

Abstract: Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetylmorphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing.

Scopolamine- and morphine-induced impairments of spontaneous alternation performance in mice: reversal with glucose and with cholinergic and adrenergic agonists.

Abstract: Administration of epinephrine and glucose, as well as drugs that influence cholinergic and opiate systems, can enhance or impair memory. The present experiments examined the possibility that peripheral glucose administration might reverse scopolamine- and morphine-induced impairments in a spontaneous alternation task. Mice received all drug administrations 30 min before testing. Scopolamine-induced (3 mg/kg) deficits in alternation performance were reversed by glucose (100 and 250 mg/kg), amphetamine (1 mg/kg), epinephrine, physostigmine, and oxotremorine (each 0.1 mg/kg). Morphine (10 mg/kg) also impaired spontaneous alternation performance, and glucose (100 and 300 mg/kg) reversed this impairment as well. These findings are consistent with the view that central cholinergic systems, possibly under inhibitory opiate regulation, may contribute to glucose and epinephrine effects on memory storage.

Interaction between opiate subtype and alpha-2 adrenergic agonists in suppression of noxiously evoked activity of WDR neurons in the spinal dorsal horn.

Abstract: Several studies have demonstrated synergistic antinociception following low-dose administration of morphine and alpha-2 adrenergic agonists at the spinal level This study was carried out in order to identify the opiate subtypes that are likely to be involved in such synergistic suppression of noxiously evoked activity of wide-dynamic-range (WDR) neurons in the dorsal horn of the spinal cord We also examined the effect of opiate antagonists and alpha-2 adrenergic antagonists on the suppression produced by opiate or alpha-2 adrenergic agonists Extracellular activity of single WDR neurons in the spinal dorsal horn, which was evoked by a radiant heat stimulus (51 degrees C), was recorded in decerebrate, spinally transected cats Agonists were administered spinally and antagonists intravenously In the synergism study, ineffective doses of the moderately selective mu agonist morphine (25 micrograms), the delta agonist DADL (20 micrograms), and the selective delta agonist DPDPE (30 micrograms), when combined with an ineffective dose of the alpha-2 adrenergic agonist clonidine (5 micrograms) produced significant synergistic suppression of noxiously evoked WDR neuronal activity However, the ineffective or slightly effective dose of the selective mu agonist DAGO (1 or 15 micrograms, respectively) did not show any synergistic action with clonidine Furthermore, the synergism between morphine and clonidine was reversed by the selective delta antagonist ICI 174,864 We interpret these results to indicate that opiates interact at spinal delta receptors to produce a synergistic suppression of evoked WDR neuronal activity in the presence of spinal clonidine An alternative explanation is that ICI 174,864 may interact in some way with alpha-adrenergic systems(ABSTRACT TRUNCATED AT 250 WORDS)

Forensic Drug Testing for Opiates, III. Urinary Excretion Rates of Morphine and Codeine Following Codeine Administration

Abstract: The urinary excretion profile of free and conjugated codeine and morphine was determined by GC/MS for four healthy male subjects after intramuscular administration of 60- and 120-mg doses of codeine. Codeine and metabolites were rapidly excreted with the majority of drug appearing in the first 24 h. No dose-related differences in metabolism were observed. The initial ratio of total codeine to total morphine was substantially greater than 1.0 but declined over time. For two of the four subjects, the codeine-morphine ratio declined below 1.0 late in the elimination phase. With a 300-ng/mL cutoff, one subject tested positive on more than one occasion for total morphine and negative for codeine during the terminal elimination phase. The data indicate that urine codeine-morphine ratios are not reliable indices of the type of opiate exposure.

Endogenous opioids: do they modulate the rat pup's response to social isolation?

Abstract: Previous studies with several different species have suggested that opioids and their receptors are involved in the mediation of the infant's vocal response to social isolation In the case of the rat pup, 2 models have been hypothesized to relate opioids and the ultrasonic call emitted during social isolation One model views the comforting effects of social contact as opioid mediated and the apparent distress of social isolation as analogous to opiate withdrawal The 2nd model considers social separation as a stressor that recruits endogenous opioids This article describes 3 experiments that tested both of these models in 7-10-day-old rat pups In Experiment 1, morphine (004-040 mg/kg) decreased the rate of isolation calls in a dose-dependent, naloxone-reversible fashion However, the decrease in calling rate was observed only at doses that decreased locomotor activity Administration of the reversible opiate antagonist naloxone (005-50 mg/kg) did not alter the rate of calls during either 2- or 6-min isolation tests at either 24 or 32 degrees C In Experiment 2, the irreversible mu opioid receptor antagonist beta-funaltrexamine (beta-FNA) was administered into the lateral ventricle of 6-day-old pups Again, no change in the rate of isolation calls was found, although sensitivity to morphine was markedly decreased, and mu (but not delta or kappa) receptors were decreased in selected brain regions by about 40% In Experiment 3, in vivo receptor binding was used to directly investigate the availability of mu opioid receptors during social contact and social isolation Pups injected with 3H-diprenorphine showed relatively high levels of specific in vivo binding that followed the regional pattern of in vitro binding, but no effects of social isolation were apparent in the 5 brain regions assayed Taken together, the consistent negative results with opiate receptor antagonists, as well as the inability to detect an alteration of in vivo binding, suggest that the mu opioid receptor is not an essential part of the rat pup's vocal response to social separation

Excitatory amino acids and morphine withdrawal: differential effects of central and peripheral kynurenic acid administration.

Abstract: The non-selective excitatory amino acid antagonist kynurenic acid, which does not readily cross the blood-brain barrier, dose-dependently attenuated the behavioral signs of naltrexone-precipitated withdrawal in morphine-dependent rats following both intraventricular and subcutaneous administration. However, intraventricular and subcutaneous administration of kynurenic acid and different effects on individual withdrawal behaviors. Moreover, single unit recordings in anesthetized animals showed that intraventricular, but not subcutaneous, kynurenic acid administration attenuated the withdrawal-induced increased firing of locus coeruleus neurons. These studies indicate that: (1) both central and peripheral excitatory amino acid receptors may play an important role in opiate withdrawal; and (2) excitatory amino acid antagonist treatments might be developed to reduce opiate abstinence symptoms in man.

Predictors of opiate drug abuse during a 90-day methadone detoxification.

Abstract: The behavioral circumstances related to opiate drug use were examined during a 90-day outpatient methadone detoxification. Seventy-one subjects (55 male and 16 female) were followed from the day of intake to treatment termination. Data were collected by means of a weekly structured interview. Questions were asked about each occasion of opiate use in the previous week with respect to time, source, cost, social circumstance, etc. Monitored urine samples were tested x3/week to verify verbal reports. The study demonstrated beneficial effects of the detoxification treatment by showing dramatic decreases in rates and amounts of opiate drug use during treatment. The study also identified race (p <. 0008; t = -3.522; beta = -0.366), gender (p <. 0243; t = 2.305; beta = 0.222), and the number of opiate use episodes/week at baseline (p <. 0013; t = -3.364; beta = -0.338) as significant and independent predictors of treatment outcome. Current duration of regular and continuous opiate use was also found to be...

Effect of prenatal cocaine on respiration, heart rate, and sudden infant death syndrome†

Abstract: We studied 114 neonates by pneumocardiogram recordings in order to examine the effects of cocaine with and without opiate exposure on neonatal respiration, heart rate, apparent life threatening events (ALTE), and sudden infant death syndrome (SIDS). In full-term infants exposed to cocaine without opiates we found increased longest apnea duration and more episodes of bradycardia, but decreased periodic breathing and average heart rate than in control full-term infants. Term infants prenatally exposed to cocaine with opiates also had less periodic breathing. Preterm infants exposed to cocaine with and without opiates had decreased apnea density and periodic breathing compared with preterm controls. Discriminant analysis to determine whether perinatal asphyxia or exposure to other drugs could predict cardiorespiratory abnormalities showed no consistent relationship. In 72 of 114 infants available for follow-up, no ALTE occurred but two were lost to SIDS. Our data support the hypothesis that prenatal cocaine exposure may perturb, albeit subtly, the maturation of respiratory control, resulting in disruption of postnatal respiration.

Poppy seed ingestion as a contributing factor to opiate-positive urinalysis results: the Pacific perspective.

Abstract: The possible contribution of poppy seed foods to positive opiate urinalysis results, especially from foods available in the Pacific Rim area, has recently become an issue for the U.S. Army Forensic Toxicology Drug Testing Laboratory in Hawaii. To assess the likelihood of this possible contribution, seven different poppy seed food products were consumed by male and female volunteers, and urine specimens were collected at time increments up to either 24 or 72 h. Specimens were evaluated for opiates using Roche Abuscreen radioimmunoassay (RIA), and all RIA positive specimens were analyzed for morphine and codeine using gas chromatography/mass spectrometry (GC-MS). Poppy seed cake, bagels, muffins, and rolls did not contain sufficient quantities of poppy seeds to give rise to opiate positive specimens by U.S. Department of Defense (DOD) GC-MS cutoff levels (morphine = 4000 ng/mL, codeine = 2000 ng/mL), although a number of specimens were positive by National Institute on Drug Abuse (NIDA) cutoff levels (morphine and codeine = 300 ng/mL). However, ingestion of poppy seed streusel or Danish pastry led to confirmed morphine and codeine positive specimens, irrespective of the use of DOD or NIDA confirmation cutoff values. In addition, significant amounts of codeine were observed in a number of these specimens. These findings argue against the unqualified application of previously published quantitative guidelines for eliminating poppy seed ingestion as a possible cause for a positive opiate urinalysis result.

Changes of endogenous morphine and codeine contents in the fasting rat.

Abstract: The alteration of endogenous opiate alkaloids during fasting state was investigated in rats. The concentrations of morphine and codeine in the cortex, midbrain, pons plus medulla, cerebellum, adrenal gland and pancreas were measured using radioimmunoassay for the opiates following high pressure liquid chromatography. The morphine and codeine contents of fasting rats showed maximum elevated levels in cortex, pons plus medulla and pancreas after 2 days of fasting, but after 1 day in midbrain. The opiate content of the cerebellum showed a tendency for a continuous increase during the 4 days. Adrenal glands of fasting rats had elevated levels at days 3 and 4, although there were great fluctuations within the groups.

Self-detoxification by opiate addicts. A preliminary investigation.

Abstract: A study of 50 opiate addicts attending a London service for treatment of drug dependence found that 47 subjects had previously made at least one attempt at self-detoxification. These subjects reported 212 previous attempts. Although 30 subjects reported having managed to complete at least one attempt, the success rate per episode was low (24%). One of the most commonly reported methods, used by 28 subjects, involved an abrupt cessation of opiates ('cold turkey'). Of the drugs used in their attempts at self-detoxification, benzodiazepines were reported by 24 subjects and opiates by 20. Practical strategies such as distraction and avoidance were also used. Self-help detoxification materials for opiate addicts might be useful.

Multiple opiate receptors of brain and spinal cord in opiate addiction.

Abstract: 1. Chronic administration of opiates to rodents results in the development of tolerance to their pharmacological effects. Physical dependence also develops and is shown by the appearance of abstinence syndrome. 2. Opiates produce their effects by acting on three types of opiate receptors, namely mu, delta and kappa. The qualitative and quantitative aspects of the tolerance-dependence and abstinence symptoms observed after chronic administration of agonists acting at mu-, delta- and kappa-opiate receptors appear to differ. 3. Tolerance-dependence on mu-opiate agonists, such as morphine, is associated with down-regulation of mu-opiate receptors in spinal cord and specific areas of the brain but delta- and kappa-opiate receptors are unchanged. During abstinence from mu-opiate agonists, brain and spinal cord mu-, delta- and kappa-opiate receptors are unaffected. 4. Chronic administration of kappa-opiate agonists, such as U-50,488H, results in the development of tolerance to its pharmacological effects and a mild degree of physical dependence. Such changes are associated not only with alterations of delta and kappa opiate receptors in brain and spinal cord, but also primarily with a down-regulation of kappa-opiate receptors in spinal cord and specific brain regions. mu-Opiate receptors are unaffected. 5. Chronic administration of delta-opiate agonists results in down-regulation of brain delta-opiate receptors. 6. It is concluded that tolerance-dependence on mu-, delta- and kappa-opiate receptors is associated with down-regulation of their own type of receptors in the spinal and supraspinal areas. Abstinence, on the other hand, does not alter brain and spinal cord opiate receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

EEG evidence that morphine and an enkephalin analog cross the blood-brain barrier.

Abstract: The ability of naltrexone but not methyl naltrexone to cross the blood-brain barrier (BBB) was used to provide a different approach for the demonstration that opiates can enter the brain. Cortical electroencephalographic (EEG) measurements were made in rats receiving peripheral (IP) injections of naltrexone or methyl naltrexone and morphine or an enkephalin analog [Tyr-D-Ala-Gly-MePhe-Met(O)-ol]. Naltrexone significantly blocked the EEG effects of morphine and the enkephalin analog, but methyl naltrexone failed to do so. The results provide biological evidence that an opiate peptide can cross the BBB to affect the activity of the brain.

Opioid-dependent behaviors in infant rats: effects of prenatal exposure to ethanol.

Abstract: Pregnant rats were given diets containing either 5% ethanol, an isocaloric (pair-fed) diet, or casein pellets. Offspring were tested at postnatal day 10 for isolation-induced ultrasonic vocalizations and subsequent stress-induced analgesia. Rats prenatally exposed to ethanol vocalized significantly less in the five minutes during isolation. The opiate, morphine, caused a greater suppression of vocalizations in alcohol-exposed pups compared to controls, while the increased calling normally seen with the opiate antagonist, naltrexone, was attenuated. In a test in which the pup withdraws a paw from a hot plate (48 degrees C), prenatal alcohol offspring demonstrated baseline latencies (no isolation) similar to controls but had greatly attenuated responses in their isolation-induced analgesia. Since both vocalization and analgesia responses have been determined to be modulated by the endogenous opioid system, the aberrant responses of the prenatal-ethanol-exposed offspring can be interpreted as failures to respond by opioid release/secretion to appropriate stimuli.

Opiate-dopamine interactions in the neural substrates of acoustics startle gating in the rat

Abstract: Swerdlow, Neal R.S. Barak Caine and Mark A. Geyer: Opiate-dopamine interactions in the neural substrates of acoustic startle gating in the rat. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1991, 15 : 415–426. 1. 1. The acoustic startle reflex (ASR) was measured in adult male Dawley rats using startling acoustic stimuli presented either alone or 60–500 msec after a weak acoustic prepulse. 2. 2. The inhibition of the ASR by the prepulse, termed “prepulse inhibition” (PPI), was blocked in animals treated either with the indirect dopamine (DA) agonlst d-amphetamine (AMPH) or with the direct DA receptor agonist apomorphlne (APO). 3. 3. Pretreatment with the opiate receptor antagonist naloxone (NAD prevented the AMPH-induced loss of PPI, but did not diminish the APO-induced loss of PPI. 4. 4 The opiate heroin had no significant effect on PPI. 5. 5. Dopaminergic mechanisms that modulate PPI in the rat may be regulated by opiate systems that act presynaptic to the DA receptor; brain opiate receptors may not have direct effects on startle gating independent of this opiate-DA interaction.