Cellular site of opiate dependence
NaturePublished 1 February 1980
H. O. J. COLLIER
Citations199
SJR quartileQ1
SJR score18.29
SNIP10.16
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
It is shown that opiate dependence and associated tolerance develop within neurones bearing specific opiate receptors (opiate-sensitive neurones) within the cyclic AMP system in response to inhibition by opiate of a neuronal adenylate cyclase.
Abstract
Experiments on whole animals, guinea pig isolated ileum, individual neurones in situ and cultured neuroblastoma--glioma hybrid cells indicate that opiate dependence and associated tolerance develop within neurones bearing specific opiate receptors (opiate-sensitive neurones). The essential change appears to be an hypertrophy of the cyclic AMP system, in response to inhibition by opiate of a neuronal adenylate cyclase.
Keywords
NeuroscienceBiochemistry, Genetics and Molecular Biology
ScienceOpiate Receptor: Demonstration in Nervous Tissue
2,374 Citations1973Candace B. Pert, Solomon H. Snyder
Tritiated naloxone, a powerful opiate antagonist, specifically binds to an opiate receptor of mammalian brain and guinea pig intestine that closely parallels their pharmacological potency.
Trends in Biochemical SciencesOpiates and endogenous opioid peptides
1,291 Citations1977John Kelly, Raymond Dingledine
Proceedings of the National Academy of SciencesStereospecific Binding of the Potent Narcotic Analgesic [ <sup>3</sup> H]Etorphine to Rat-Brain Homogenate
1,064 Citations1973Eric J. Simon, Jacob M. Hiller +1 more
Etorphine, the most potent narcotic analgesic known, was labeled with tritium by catalytic exchange and exhibits stereospecific, saturable binding to rat-brain homogenate.
Journal of Pharmacology and Experimental TherapeuticsSIMULTANEOUS QUANTITATIVE ASSESSMENT OF MORPHINE TOLERANCE AND PHYSICAL DEPENDENCE
680 Citations1969E. Leong Way, HORACE H. LOU +1 more
Proceedings of the National Academy of SciencesDual regulation of adenylate cyclase accounts for narcotic dependence and tolerance.
669 Citations1975S K Sharma, Werner A. Klee +1 more
The coupled inhibitory and positive regulatory mechanisms for adenylate cyclase provide a means of activating and deactivating neural circuits hours after the initial event and thus may play a role in a memory process.
NatureHigh-affinity enkephalin-degrading peptidase in brain is increased after morphine
650 Citations1978Bernard Malfroy, Jean-Paul Swerts +3 more
The presence of a high-affinity peptidase in a particulate fraction of mouse striatum splitting the Leu-enkephalin molecule with release of a tripeptide fragment and exhibiting definite substrate specificity suggests that it might be associated with enkphalinergic transmission.
ScienceOpioid Peptides May Excite Hippocampal Pyramidal Neurons by Inhibiting Adjacent Inhibitory Interneurons
611 Citations1979W. Zieglgänsberger, E. D. French +2 more
The results suggest that the opioids excite pyramidal neurons indirectly by inhibition of neighboring inhibitory interneurons (probably containing gamma-aminobutyric acid).
Proceedings of the National Academy of SciencesMorphine receptors as regulators of adenylate cyclase activity.
531 Citations1975S K Sharma, Marshall W. Nirenberg +1 more
Morphine inhibits adenylate cyclase (EC 4.6.1.1) activity of neuroblastoma times glioma hybrid cells, and the degree of sensitivity was shown to be dependent upon the abundance of narcotic receptors.
International review of cytologyStructural, Electrophysiological, Biochemical, and Pharmacological Properties of Neuroblastoma-Glioma Cell Hybrids in Cell Culture
385 Citations1977Bernd Hamprecht
This chapter discusses the structural, electrophysiological, biochemical and pharmacological properties of neuroblastoma-glioma cell hybrids in cell culture and the rescue of latent viruses and the genetic analysis of malignancy and of viral gene expression.
NatureMorphine-like drugs inhibit the stimulation by E prostaglandins of cyclic AMP formation by rat brain homogenate
377 Citations1974H. O. J. COLLIER, A.C. Roy
In homogenate of rat brain, morphine, at concentrations obtainable in vivo, inhibited the stimulation by prostaglandin E1 or E2 of cyclic AMP formation, without inhibiting the basal production of cyclIC AMP.
Proceedings of the National Academy of SciencesA Neuroblastoma × Glioma Hybrid Cell Line with Morphine Receptors
317 Citations1974Werner A. Klee, Marshall W. Nirenberg
A neuroblastoma × glioma hybrid cell line with well-developed neural properties was found that has high-affinity morphine receptors, in contrast to parent cells and other Neuroblastoma or hybrid cell lines tested that had few or no morphine receptors.
ProstaglandinsII - Prostaglandin hyperalgesia: The peripheral analgesic activity of morphine, enkephalins and opioid antagonists
314 Citations1979S. H. Ferreira, Meire Nakamura
It was suggested that the peripheral analgesic effect of morphine is due to an inhibition of adenylate-cyclase activity.
Proceedings of the National Academy of SciencesNeuronal actions of endorphins and enkephalins among brain regions: a comparative microiontophoretic study.
301 Citations1977Roger A. Nicoll, George R. Siggins +3 more
Results are consistent with the hypothesis that the endorphins and enkephalins may represent a new class of central neurotransmitters; among other functions, these peptides may play a role in the regulation of behavior and the expression of psychopharmacological agents such as the opiate alkaloids.
NatureAdenosine inhibits the accumulation of cyclic AMP in cultured brain cells
246 Citations1978Dietrich van Calker, Margarete Müller +1 more
It is reported here that the inhibition by adenosine of the increase in the intracellular level of cyclic AMP evoked by isoprenaline in cultured glioblasts is mediated by extracellular receptors.
NatureModification of Morphine Withdrawal by Drugs interacting with Humoral Mechanisms: Some Contradictions and their Interpretation
234 Citations1972H. O. J. COLLIER, David Francis +1 more
These findings suggest that morphine dependence is multipartite and that acetylcholine, 5-hydroxytryptamine and prostaglandin(s) play intimate parts in various elements of dependence.
ScienceStereospecific and Nonstereospecific Effects of (+)- and (—)-Morphine: Evidence for a New Class of Receptors?
165 Citations1977Yasuko F. Jacquet, Werner A. Klee +3 more
The unnatural (+) enantiomer of morphine had minimal activity in three opiate assays in vitro: the rat brain homogenate binding assay, the electrically stimulated guinea pig ileum assay, and the inhibition of adenylate cyclase in neuroblastoma X glioma hybrid cell homogenates.
British Journal of PharmacologyMorphine‐tolerant longitudinal muscle strip from guinea‐pig ileum
155 Citations1973A Goldstein, Rüdiger Schulz
Electrically evoked contractions of the myenteric plexus‐longitudinal muscle preparations from tolerant animals showed reduced sensitivity to the depressant effects of adrenaline, isoprenaline, and particularly, dopamine.
NatureHypersensitivity to noradrenaline in cortex after chronic morphine: relevance to tolerance and dependence
129 Citations1978Catherine Llorens‐Cortés, Marie‐Pascale Martres +2 more
It is reported here that opiate receptors are presynaptically localised on noradrenergic neurones as indicated by their depletion in cortex and cerebellum after a selective degeneration of these neurones, and that chronic treatment with morphine is followed by an increased responsiveness of the cortical cyclic AMP system to catecholamines, accompanied by anincreased number of β- adrenergic receptors.
NatureMorphine abstinence is associated with increased brain cyclic AMP
128 Citations1975H. O. J. COLLIER, David Francis
These experiments indicated that cyclic AMP rather than cyclic GMP was primarily involved in the abstinence syndrome, and attempted to identify the nucleotide by intracere-broventricular injection of cyclic nucleotides.
Journal of Pharmacology and Experimental TherapeuticsTOLERANCE TO OPIOID NARCOTICS. I. TOLERANCE TO THE "RUNNING FIT" CAUSED BY LEVORPHANOL IN THE MOUSE
122 Citations1969Avram Goldstein, Patricia Sheehan
The running fit induced by opioid narcotics in mice serves as a convenient graded measure of the effect of these drugs and a high degree of stereospecificity has been demonstrated by using D(—)-levorphanol and its L(+)-isomer.
Life SciencesAspects of opiate dependence in the myenteric plexus of the guinea-pig
117 Citations1976Rüdiger Schulz, Albert Herz
The data confirms a close relationship between a state of tolerance and dependence (including display of the abstinence sign) and supersensitivity to putative neurotransmitters or neuromodulators, becoming evident following administration of naloxone.
Life SciencesInfluence of opiates on the levels of adenosine 3′ : 5′-cyclic monophosphate in neuroblastoma x glioma hybrid cells
115 Citations1975J. Traber, R J Gullis +1 more
The increased response to PGE 1 is discussed in connection with morphine tolerance and withdrawal in neuroblastoma x glioma hybrid cells.
NatureTolerance to Opioid Narcotics: Time Course and Reversibility of Physical Dependence in Mice
105 Citations1971D.L. Cheney, Avram Goldstein
This work has used the method of jumping behaviour elicited by the opiate antagonist, naloxone, to follow the time courses of the onset and reversal of dependence in various conditions of exposure to opiates.
Brain ResearchActions of opiates upon single unit activity in the cortex of naive and tolerant rats
89 Citations1976Masamichi Satoh, W. Zieglgänsberger +1 more
The present data speak in favour of a postsynaptically located stereospecific receptor which mediates the inhibitory effects of opiates and which may be involved in the development of acute and chronic tolerance to these drugs.
NatureMorphine Tolerance and Supersensitivity to 5-Hydroxytryptamine in the Myenteric Plexus of the Guinea-pig
77 Citations1973Rainer Schulz, A Goldstein
Investigation in several laboratories have shown that the morphine receptors in this neural network are like those in the central nervous system in all the following essentials: the effective concentrations of morphine are very low, of the order of 20–100 nM.
NatureOpiate tolerance and dependence induced in vitro in single myenteric neurones
58 Citations1978R. Alan North, P J Karras
The present experiments have induced tolerance to the effects of opiates by exposing myenteric neurones to agonists in vitro for periods of about 24 h, and such neurones also showed manifestations of dependence on the presence of the opiate.
Life SciencesMorphine abstinence and quasi-abstinence effects after phosphodiesterase inhibitors and naloxone
57 Citations1975David Francis, A.C. Roy +1 more
It is indicated that morphine-abstinence effects express increased activity of a central cyclic AMP mechanism and naloxone can potently stimulate behavior in animals not treated with any opiate drug.
Life SciencesAcute tolerance to the excitatory effect of enkephalin microinjections into hippocampus
56 Citations1979Zeev Elazar, E Motles +2 more
It is suggested that acute tolerance may develop to the epileptogenic effect of leu-enkephalin in hippocampus.
NatureIs adenosine the mediator of opiate action on neuronal firing rate?
49 Citations1979Trevor W. Stone, M.N. Perkins
It is found that aminophylline will block responses to both morphine and adenosine, suggesting that the depressant responses to morphine may also be mediated by the local release ofadenosine.
Brain ResearchInteraction of morphine, etorphine and enkephalins with dopamine-stimulated adenylate cyclase of monkey amygdala
48 Citations1979Stanley A. Walczak, Doug Wilkening +1 more
It is postulated that the inhibition involves interaction of opiate receptors with catalytic units of dopamine-stimulated AC, but not with other cyclase species which may provide the major component of Gpp(NH)p- Stimulated activity in amygdala.
British Journal of PharmacologyTHE OFFSET OF MORPHINE TOLERANCE IN RATS AND MICE
48 Citations1975Brian M. Cox, M. Ginsburg +2 more
During the period following a tolerance‐inducing pretreatment with morphine in mice, the rate of attenuation of the naloxone‐evoked jumping response was faster than the rateof offset of tolerance, and a biphasic recovery of analgesic responsiveness was seen.
NatureApomorphine and morphine stimulate prostaglandin biosynthesis
47 Citations1974H. O. J. COLLIER, Wendy J. McDonald-Gibson +1 more
Experiments showing that both apomorphine or morphine stimulate, although possibly in a somewhat different way, the prostaglandin (PG) synthetase of bull seminal vesicles are described.
Life SciencesProstaglandins, cyclic AMP and the mechanism of opiate dependence
42 Citations1975H. O. J. COLLIER, David Francis +3 more
It is shown that opiate dependence is a state of heightened potential activity of a neuronal cyclic AMP mechanism, initiated and maintained by the blockade of an adenylate cyclase.
British Journal of PharmacologyTHE INHIBITORY EFFECTS OF PRESYNAPTIC α‐ADRENOCEPTOR AGONISTS ON CONTRACTIONS OF GUINEA‐PIG ILEUM AND MOUSE VAS DEFERENS IN THE MORPHINE‐DEPENDENT AND WITHDRAWN STATES PRODUCED <i>in vitro</i>
42 Citations1979Maureen Gc Gillan, H. W. Kosterlitz +2 more
A possible explanation is suggested for the loss of the inhibitory effects of presynaptic α‐adrenoceptor agonists in the withdrawn state of the dependent ileum.
British Journal of PharmacologyMETHYL XANTHINES, ADENOSINE 3′,5′‐CYCLIC MONOPHOSPHATE AND THE SPINAL TRANSMISSION OF NOCICEPTIVE INFORMATION
40 Citations1979A.W. Duggan, B.T. Griersmith
Results in the spinal cord do not support the hypothesis that the inhibition of synthesis of cyclic AMP is relevant to the analgesic action of morphine in mammals.
European Journal of PharmacologyMechanism of quasi-morphine withdrawal behaviour induced by methylxanthines
36 Citations1979NAEEM M. BUTT, H. O. J. COLLIER +3 more
Of 7 phosphodiesterase inhibitors tested for ability to induce a quasi-morphine withdrawal syndrome in opiate-naive rats, five were effective in a dose-related way and their potencies in inducing a QMWS correlated significantly with those in inhibiting low Km cyclic AMP phosphodiesters of rat brain homogenate.
British Journal of PharmacologyINHIBITION OF NEURONAL FIRING BY OPIATES: EVIDENCE AGAINST THE INVOLVEMENT OF CYCLIC NUCLEOTIDES
36 Citations1979P J Karras, R. Alan North
The results lend no support to the notion that a reduction in intracellular cyclic AMP is essential to the inhibition of firing produced by morphine.
Brain ResearchEffect of opioid peptides onl-noradrenaline-stimulated cyclic AMP formation in homogenates of rat cerebral cortex and hypothalamus
35 Citations1978D. Tsang, A. T. Tan +2 more
The data suggest that in rat cerebral cortex and hypothalamus opiates bind to opiate receptors and that the opiate-receptor complex interferes with noradrenergic receptor activity.
Life SciencesEffects of morphine on dopamine-stimulated adenylate cyclase and on cyclic GMP formation in primate brain amygdaloid nucleus
33 Citations1976Doug Wilkening, Ram K. Mishra +1 more
British Journal of PharmacologyComparison of effect of morphine‐like analgesics on transmurally stimulated guinea‐pig ileum
30 Citations1969M. R. Fennessy, R L H HEIMANS +1 more
Morphine‐like analgesic drugs caused depression of twitches of the isolated guinea‐pig ileum in response to transmural electrical stimulation and tolerance to the drug and dependence on it did not occur, and these observations have been discussed in relation to analgesic activity, tolerance and dependence in man.
The Japanese Journal of PharmacologyMORPHINE-INDUCED CHANGES IN CYCLIC AMP METABOLISM AND PROTEIN KINASE ACTIVITY IN THE BRAIN
18 Citations1978Kinya Kuriyama, Kazuo Nakagawa +2 more
Biochemical and Biophysical Research CommunicationsInhibition by beta-endorphin of dopamine-sensitive anenylate cyclase in rat striatum
17 Citations1977T Motomatsu, Martin Lis +2 more
Beta-LPH 61–91 (beta-endorphin) inhibited the basal and dopamine-stimulated adenylate cyclase activity in a homogenate of rat striatum and Naloxone prevented this effect.
Naunyn-Schmiedeberg s Archives of PharmacologyInteractions of opiates and prostaglandins E with regard to cyclic AMP in striatal tissue of rats in vitro
17 Citations1978U. Havemann, K. Kuschinsky
It is suggested that under some experimental conditions described in the literature, endogenous activators of cAMP formation, e.
Annals of the New York Academy of SciencesRESPONSIVITY TO NALOXONE DURING MORPHINE DEPENDENCE
16 Citations1976E. Leong Way, Horace H. Loh
The Nalline test, named after the trade name of the drug, was widely used in the State of California in the 1960's to detect narcotic usage in narcotic probationers and parolees and indicated that the intensity of the nalorphine-precipitated withdrawal signs was related to the degree of physical dependence in the addict and the n alorphine dose.
Canadian Journal of Physiology and PharmacologyCerebellar cAMP levels following acute and chronic morphine administration
10 Citations1977Kyriakos Charalampous, William E. Askew
Acute administration of morphine sulfate at 20 mg/kg decreased mouse cerebellar adenosine 3',5'-cyclic phosphate levels while not affecting cAMP phosphodiesterase while Propanolol prevented the cAMP increase during abrupt withdrawal.
Brain Researchβ-endrophin: modulation of acute tolerance and antagonism by endogenous brain systems
7 Citations1978Yasuko F. Jacquet, Werner A. Klee +1 more