Showing papers on "Opiate published in 1992"
TL;DR: Gaetano Di Chiara and Alan North argue that both dopaminergic and non-dopaminergic systems are involved in opiate reward, and that opiate addiction results from adaptive and learning processes involving both positive reinforcing mechanismsrelated to the rewarding properties of opiates and negative reinforcing mechanisms related to the aversive properties of withdrawal in dependent subjects.
548 citations
TL;DR: It is suggested that cocaine-related stimuli evoke Pavlovian conditioned responses in cocaine abuse patients, and such findings encourage continuing efforts to develop drug treatment strategies based on conditioning principles.
Abstract: Subjects with a history of free-basing and smoking cocaine but no history of opiate injections were exposed to three sets of stimuli. They received cocaine-related stimuli in one session, opiate-related stimuli in a second session, and non-drug stimuli on a third occasion. Compared to the opiate and non-drug cues, the cocaine-related events caused reliable decreases in skin temperature and skin resistance, and reliable increases in heart rate, self-reported cocaine craving, and self-reported cocaine withdrawal. Furthermore, control subjects lacking a history of cocaine or opiate use failed to show such differential responding. These results suggest that cocaine-related stimuli evoke Pavlovian conditioned responses in cocaine abuse patients. Such findings encourage continuing efforts to develop drug treatment strategies based on conditioning principles.
434 citations
TL;DR: The results indicate that repeated morphine administration induces a state of dependence in DA neurons and a short‐lasting tolerance followed by an increased sensitivity to its stimulant effects on DA transmission, which might play an important role in the development of opiates addiction and in the maintenance of opiate self‐administration in dependent subjects.
Abstract: To investigate the role of mesolimbic dopamine (DA) in the mechanism of drug dependence, extracellular DA was monitored by transcerebral dialysis in the caudal nucleus accumbens under basal conditions and after challenge with morphine (5 mg/kg s.c.) in control rats and in rats made dependent on and then deprived of morphine. Withdrawal from morphine resulted in a marked reduction of extracellular DA concentrations from control values at 1, 2, 3, and 5 days of withdrawal. After 7 days of withdrawal, DA output was less, but still significantly, reduced. Challenge with morphine resulted in stimulation of DA output in controls (maximum, 35%), no effect on the first day of withdrawal, and stimulation similar to controls’ on days 2 and 7 of withdrawal. On day 5 and, particularly, on day 3 of withdrawal, morphine-induced stimulation of DA output was markedly potentiated (maximum, 100 and 160%, respectively). Changes in the sensitivity of DA transmission to morphine challenge were associated with changes in the behavioral stimulant effects of morphine, with tolerance on day 1 and marked sensitization on days 3 and 5 but also on day 7, when morphine-induced stimulation of transmission was no longer potentiated. The results indicate that repeated morphine administration induces a state of dependence in DA neurons and a short-lasting tolerance followed by an increased sensitivity to its stimulant effects on DA transmission. These changes might play an important role in the development of opiate addiction and in the maintenance of opiate self-administration in dependent subjects.
221 citations
TL;DR: It is shown that acute morphine decreases the state of phosphorylation of CREB, an effect that becomes completely attenuated after chronic morphine administration, which could be part of the molecular pathway by which opiates produce changes in gene expression that lead to addiction.
Abstract: Previous studies have implicated adaptations in the cyclic AMP system in mechanisms of opiate tolerance, dependence, and withdrawal in the rat locus coeruleus. It has been speculated that such adaptations may occur at the level of gene expression. To understand better the mechanism by which opiates produce these intracellular adaptations, we studied morphine regulation of the state of phosphorylation of cyclic AMP response element-binding protein (CREB), a transcription factor that mediates some of the effects of the cyclic AMP system on gene expression. We show here, by use of a back phosphorylation and immunoprecipitation procedure, that acute morphine decreases the state of phosphorylation of CREB, an effect that becomes completely attenuated after chronic morphine administration. In contrast, acute precipitation of opiate withdrawal, via administration of an opiate receptor antagonist, increases the phosphorylation state of CREB. Such regulation of CREB phosphorylation could be part of the molecular pathway by which opiates produce changes in gene expression that lead to addiction.
206 citations
Journal Article•
TL;DR: Although pretreatment with morphine somewhat enhanced the effects of delta 9-THC, pretreatment of the mice with naloxone failed to block the antinociceptive effects of the cannabinoids, indicating that the cannabinoid-induced ant inociception does not occur due to direct interaction with the opiate receptor.
Abstract: The antinociceptive effects of various cannabinoids, alone and in combination with opiates, were evaluated in antinociceptive tests in mice. The cannabinoids tested produce marked antinociceptive effects after i.t. administration to mice. The rank order of potency for the drugs using the tail-flick test was levonantradol greater than CP-55,940 = CP-56,667 greater than 11-hydroxy-delta 9-THC greater than delta 9-THC greater than delta 8-THC; dextronantradol was inactive at a dose of 25 micrograms/mouse. Respective ED50 values in the tail-flick test were 0.4, 12.3, 4.2, 15, 45 and 72 micrograms/mouse. Although pretreatment with morphine somewhat enhanced the effects of delta 9-THC, pretreatment of the mice with naloxone (1 mg/kg s.c. or 1 micrograms/mouse i.t.) failed to block the antinociceptive effects of the cannabinoids, indicating that the cannabinoid-induced antinociception does not occur due to direct interaction with the opiate receptor. Pretreatment of mice with 3.13 micrograms/mouse and 6.25 micrograms/mouse of delta 9-THC shifted the ED50 of morphine to 0.15 and 0.05 micrograms/mouse, respectively (a 4-and a 12-fold shift). The shifts in the dose-response curve of the morphine were parallel. Naloxone administration (1 mg/kg s.c.) completely blocked the antinociceptive effects of the combination of 6.25 micrograms of delta 9-THC with morphine. The AD50 for naloxone blockade of the drug combination was 0.24 (0.06-0.94) mg/kg s.c. and the pA2 was 7.7 (6.7-8.9). The pA2 for naloxone blockade of the dimethylsulfoxide-morphine combination was 6.9 (5.7-8.1).(ABSTRACT TRUNCATED AT 250 WORDS)
190 citations
TL;DR: Environmental stimuli that signal the occurrence of aversive or dangerous events activate endogenous opiate analgesia systems and are shown to abolish the analgesic effect of morphine, even when morphine is applied directly to spinal cord.
Abstract: Environmental stimuli that signal the occurrence of aversive or dangerous events activate endogenous opiate analgesia systems. Signals for safety (the nonoccurrence of aversive events) produce the opposite and inhibit environmentally produced analgesia. Stimuli that signal safety are now shown to abolish the analgesic effect of morphine, even when morphine is applied directly to spinal cord. Further, this antiopiate effect occurs because the environmental stimulus leads to release of the neuropeptide cholecystokinin in the spinal cord. This process may contribute to the regulation of pain and the development of opiate tolerance.
149 citations
Book•
01 Jan 1992
TL;DR: Prenatal Alcohol Exposure and Human Development Effects of Prenatal Exposure to Ethanol in Cell Proliferation and Neuronal Migration Effects of Ethanol During Development on Neuronic Survival and Plasticity Foetal Ethanol Effects on Androgen-Sensitive Neural Differentiation
Abstract: Prenatal Alcohol Exposure and Human Development Effects of Prenatal Exposure to Ethanol in Cell Proliferation and Neuronal Migration Effects of Ethanol During Development on Neuronal Survival and Plasticity Foetal Ethanol Effects on Androgen-Sensitive Neural Differentiation The Structure and Function of the Endogenous Opiate Systems.
144 citations
TL;DR: None of the opiate agonists significantly potentiated responding for CR, although morphine infusion did tend to increase responding somewhat, and D-amphetamine did potentiate responding, as previously reported.
129 citations
TL;DR: Second dopaminergic opiate reward mechanism mediates morphine's alleviation of the withdrawal distress associated with abstinence in opiate-dependent animals, and neuroleptic-induced blockade of food-related motivational effects in food-deprived, but not in non-food-sated, animals suggests that the neural substrates of motivational events do not dissociate along the line between different rewarding stimuli but along the lines between deprivation and nondeprivation.
Abstract: Separate brain manipulations double dissociate two motivational mechanisms underlying the rewarding effects of opiates. Lesions of the brain stem tegmental pedunculopontine nucleus block the rewarding properties of morphine in drug-naive, but not in drug-dependent, rats. Neuroleptics (which block the action of the neurotransmitter dopamine) abolished opiate motivational effects in drug-dependent, but not in drug-naive, rats in place conditioning paradigms. This second dopaminergic opiate reward mechanism mediates morphine's alleviation of the withdrawal distress associated with abstinence in opiate-dependent animals. Furthermore, neuroleptic-induced blockade of food-related motivational effects in food-deprived, but not in food-sated (non-food-deprived), animals suggests that the neural substrates of motivational events do not dissociate along the line between different rewarding stimuli but along the line between deprivation and nondeprivation.
119 citations
TL;DR: Preliminary findings suggest that octreotide is a potent non‐opiate analgesic appropriate for long‐term intrathecal infusion and occurred in patients who had previously not obtained satisfactory pain control with systemic or intr Athecal opiates, which is consistent with a non-opiate spinal pathway.
Abstract: Somatostatin-14 has been reported to relieve severe cancer pain when given intraspinally. We have studied a stable analog, octreotide, which is suitable for long-term infusion by a drug pump. In preclinical trials in dogs, chronic intrathecal and intraventricular perfusion at 40 μg/h did not produce neurotoxicity. On the basis of these findings cancer patients with pain unrelieved by oral opiates were treated for periods of 13 to 91 days with intrathecal octreotide 5–20 μg/h. During octreotide infusion, pain scores were lower while oral opiate usage was reduced. No central or systemic side effects of intrathecal administration were seen. The pain relief occurred in patients who had previously not obtained satisfactory pain control with systemic or intrathecal opiates, which is consistent with a non-opiate spinal pathway. These preliminary findings, if confirmed, suggest that octreotide is a potent non-opiate analgesic appropriate for long-term intrathecal infusion.
111 citations
TL;DR: Findings indicate that reductions in neural sensitivity to opioids develop as females undergo repeated pregnancies and lactations, changes which affect both behavioral and endocrine functions.
Patent•
15 Jul 1992TL;DR: In this article, a motion was proposed to alleviate the tolerance to, or dependence on, an opiate analgesic by the administration of an effective amount of a selective delta opioid receptor antagonist to a human patient in need of such treatment.
Abstract: A motion provided to alleviate the tolerance to, or dependence on, an opiate analgesic, by the administration of an effective amount of a selective delta opioid receptor antagonist to a human patient in need of such treatment.
TL;DR: Dizocilpine may modify both motivational and somatic aspects of opioid withdrawal in rats made opiate dependent by the subcutaneous implantation of a 75 mg morphine pellet.
TL;DR: The endogenous peptide Tyr-MIF-1 and the blood-derived peptide hemorphin can act as agonists as well as antagonists in the guinea pig ileum and are consistent with the idea that properties of endogenous peptides as opiate antagonists are enhanced in the tolerant state.
TL;DR: Clinical data confirm the experimental evidence that pretreatment with opiates diminishes the sustained hyperexcitation of the central nervous system caused by peripheral lesions.
Abstract: The influence of opiate premedication on analgesic requirements postoperatively was investigated. Out of 98 patients with a lumbar disc prolapse 50 were premedicated with flunitrazepam orally, 48 with pethidine and triflupromazine intramuscularly. The operations were performed under inhalational anaesthesia. The average time up to the first demand for an analgesic was longer following opiate premedication (351 vs. 219 min). Only 45.8% of the patients treated with opiates demanded analgesics postoperatively, compared to 80.0% of those who had a benzodiazepine premedication (P These clinical data confirm the experimental evidence that pretreatment with opiates diminishes the sustained hyperexcitation of the central nervous system caused by peripheral lesions.
Book•
24 Nov 1992
TL;DR: Developmental Effects of Opiates: effects of Opioids on the Developing Brain and the Regulation of Nervous System Development: Evidence from In Vitro Studies is presented.
Abstract: Developmental Effects of Opiates: Effects of Opioids on the Developing Brain (R.P. Hammer, Jr.). Opiates and the Regulation of Nervous System Development: Evidence from In Vitro Studies (K.F. Hauser and A. Stiene-Martin). Reinforcing Properties of Opiates during Early Development (G.A. Barr). Ontogency and Plasticity of Opiate Systems (F.M. Leslie and S.E. Loughlin). Cellular Effects of Opiates: Opiate Receptor Regulation by Opiate Agonists and Antagonists (L.S. Brady). Anti-Opioid Peptides in Morphine Tolerance and Dependence (R.B. Rothman, H. Xu, H.-Y.T. Yang , and J.B. Long). Functional Anatomy of Opiate Withdrawal (G.F. Wooten). Opiates Influence Locus Coeruleus Neurons by Potent Indirect and Direct Actions (G. Aston-Jones, R. Shiekhattar, H. Akaoka, J. Rajkowski, and P. Kubiak). Excitatory Amino Acids Interact with Opioid Peptides to Regulate Neuronal Excitability and Gene Expression in the Rat Hippocampal Formation (J.F. McGinty). Molecular Effects of Opiates: Regulation of Opioid Peptides by Self-Administered Drugs (K.A. Trujillo, D.M. Bronstein, and H. Akil). Stimulus-Transcription Coupling at the m Opiate Receptor (M.M. Garcia and R.E. Harlan). Opiate Regulation of Signal Transduction Pathways (H.W. Harris and E.J. Nestler). Behavioral Effects of Opiates: Neurobiological Substrates of Opioid Abuse (S.I. Dworkin, L.J. Porrino, and J.E. Smith). Reinforcing Effects of Opiates-Modulation by Dopamine (E.M. Unterwalk and C. Kornetsky).
TL;DR: A study of 18 cases seen over 3 years broadly confirms the use of buprenorphine as a cheap alternative to heroin, and reports haematemesis during acute withdrawal, a symptom not reported in earlier studies.
Abstract: Buprenorphine was introduced as a potent analgesic with low abuse potential. Reports of buprenorphine abuse by opiate abusers have accumulated over the years, highlighting its use as a cheap alternative to heroin. The lower potency compared with heroin is being compensated by using a cocktail of buprenorphine with benzodiazepines or cyclizine. This study of 18 cases seen over 3 years broadly confirms these findings. Four cases reported haematemesis during acute withdrawal, a symptom not reported in earlier studies.
01 Jan 1992
TL;DR: It is shown that prior exposure of nucleus accumbens neurons to mu-selective opiates induces sensitization to the effects of amphetamine, and this effect is discussed in terms of opioid effects on dopamine transmission and second messenger systems.
TL;DR: All endogenous analgesia systems may in fact be opiate at the level of the spinal cord, and the need for a fundamental shift in conceptualizations regarding the organization and function of pain modulatory systems in particular, and opiate systems in general is suggested.
TL;DR: The data demonstrate that multiple pregnancies and lactations result in changes of MPOA opiate receptor density and of circulating hormone levels, which are discussed in terms of the concurrent changes in neural opiate sensitivity associated with multiparity.
TL;DR: The role of the NMDA receptor in mediating afferent nociceptive traffic is confined to its involvement in neuronal events mediating hyperalgesia.
Abstract: We have investigated the effects of systemic administration of two N-methyl-D-aspartate (NMDA) receptor antagonists and two opiate agonists on nociception during and after tail ischaemia in conscious rats. The two NMDA receptor antagonists, D-2-amino-5-phosphonovalerate (APV) and ketamine hydrochloride, did not alter tail flick latencies in rats not subjected to ischaemia but inhibited post-ischaemic hyperalgesia (PIH) in a dose-dependent manner. Neither of these agents impaired motor function of the rats, as assessed by rotarod performance, suggesting a purely sensory antinociceptive effect. The antinociceptive effect of APV during reperfusion following ischaemia was not antagonised by the mu-opiate receptor antagonist naloxone (1 mg/kg). The two opiate receptor agonists, morphine and pethidine, increased tail flick latencies in rats not subjected to ischaemia, inhibited PIH in a dose-dependent manner, and also caused significant motor malfunction, all in naloxone-reversible fashion. We conclude that the role of the NMDA receptor in mediating afferent nociceptive traffic is confined to its involvement in neuronal events mediating hyperalgesia.
TL;DR: The present work and the following companion paper were aimed at identifying the neuroanatomical loci at which endogenous opiates exert their analgesic effects in this tail-shock paradigm and, further, to identify which opiate receptor subtypes are involved.
TL;DR: This paper is the fourteenth installment of the annual review of research concerning the opiate system and includes papers published during 1991 involving the behavioral, nonanalgesic, effects of the endogenous opiate peptides.
TL;DR: 4 patients who developed organic hallucinosis while receiving opiate analgesics for cancer pain developed symptoms rapidly responded to haloperidol and change in the type of opiate.
Abstract: We report 4 patients who developed organic hallucinosis while receiving opiate analgesics for cancer pain. In all patients, the symptoms rapidly responded to haloperidol and change in the type of opiate. The hallucinations were exclusively visual. Cognitive status, determined by the Mini-mental State Questionnaire (MMSQ), was normal in all patients. Organic hallucinosis occasionally occurs in patients receiving opiates and can be a major source of distress for patients and their families.
TL;DR: Results from the immunoassays indicated a high degree of accuracy for determination of morphine levels, and the patterns of sensitivity and cross-reactivity were unique for each assay, indicating that a detailed knowledge of assay performance characteristics is necessary for accurate interpretation of forensic urine testing data.
Abstract: Four commercial immunoassays, TDx Opiates (TDx), Coat-A-Count Morphine in Urine (CAC), Abuscreen Radioimmunoassay for Morphine (ABUS) and Emit d.a.u. Opiate Assay (EMIT), were tested for sensitivity, specificity, and accuracy with urine specimens containing known amounts of opiates and opiate metabolites. The immunoassays were evaluated in a semiquantitative mode by comparison of morphine equivalents to GC/MS assay of free and total morphine and codeine or to target concentrations. In all cases, the apparent sensitivities of the assays were higher than those required for detection of morphine at cutoffs mandated by the Health and Human Services guidelines for testing of Federal workers. The apparent specificities of the immunoassays varied considerably. The CAC assay was found to be highly selective for free morphine, whereas TDx, ABUS, and EMIT demonstrated broad cross-reactivity with other opiates. Comparison of semiquantitative results from the immunoassays with GC/MS data indicated a high degree of accuracy for determination of morphine levels. Generally, the patterns of sensitivity and cross-reactivity were unique for each assay, indicating that a detailed knowledge of assay performance characteristics is necessary for accurate interpretation of forensic urine testing data.
TL;DR: It is concluded that the nasal route for naloxone administration is as effective as the parenteral route and is sensitive enough to identify the physically-dependent opiate user and might have a role in emergency medicine and withdrawal treatment.
TL;DR: The results obtained confirm previous data on the effects of yohimbine on morphine analgesia and reveal the importance of alpha 2-adrenergic activation in the development of opioid physical dependence.
TL;DR: Investigation of factors associated with relapse among 42 opiate addicts receiving out-patient detoxification treatment at a London drug-dependence clinic found interpersonal factors and drug-related cues were associated with lapse to opiate use.
Abstract: Relapse is a central problem in the treatment of addictive behaviour, and a specific problem in the out-patient treatment of the opiate withdrawal syndrome. This study investigated factors associated with relapse among 42 opiate addicts receiving out-patient detoxification treatment at a London drug-dependence clinic. All subjects completed a questionnaire about their social, psychological, and environmental circumstances in the week before interview, and were interviewed within the first two weeks of the programme. Forty per cent had lapsed to illicit heroin abuse within the previous week. Interpersonal factors and drug-related cues were associated with lapse to opiate use. Most subjects encountered a range of high-risk situations, such as regularly meeting other drug users and being offered drugs, and persistent negative mood states.
TL;DR: It is concluded that locomotor activity induced by morphine is mediated by opiate receptor through an indirect dopaminergic mechanism and not by atropine, phenoxybenzamine, propranolol and methergoline.
Abstract: 1. 1. The effect of morphine on locomotor activity in mice and the mechanism involved were evaluated. 2. 2. Subcutaneous (s.c.) injection of different doses of morphine (10, 20 and 40 mg kg−1) into mice induced a dose-dependent locomotor activity. 3. 3. The response to morphine was decreased in animals pretreated by the D-1 antagonist SCH 23390, the D-2 antagonist sulpiride or the opiate receptor antagonist naloxone, but not by atropine, phenoxybenzamine, propranolol and methergoline. 4. 4. The inhibitory effects of SCH 23390, sulpiride or naloxone were dose-dependent. 5. 5. Pretreatment with reserpine prevented the effect of morphine. SKF 38393 (D-1 agonist) or quinpirole (D-2 agonist) also induced locomotor activity in mice. Also this effect was decreased by reserpine pretreatment. 6. 6. Combination of SKF 38393 with quinpirole but not of morphine with SKF 38393 or quinpirole induced a high degree of locomotor activity in intact and reserpinized animals. 7. 7. It is concluded that locomotor activity induced by morphine is mediated by opiate receptor through an indirect dopaminergic mechanism.