We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Region-dependent changes in endocannabinoid transmission in the brain of morphine-dependent rats.
- Authors
GONZÁLEZ, SARA; SCHMID, PATRICIA; FERNÁNDEZ-RUIZ, JAVIER; KREBSBACH, RANDY; SCHMID, HARALD; RAMOS, JOSÉ; González, Sara; Schmid, Patricia C; Fernández-Ruiz, Javier; Schmid, Harald H O; Ramos, José A
- Abstract
It has been suggested recently that the endocannabinoid system might be a component of the brain reward circuitry and thus play a role not only in cannabinoid tolerance/dependence, but also in dependence/withdrawal to other drugs of abuse. Here we have examined the changes in endocannabinoid ligands and their receptors in different brain regions, with particular attention to those areas related to reinforcement processes, during dependence on the powerful addictive drug, morphine. Thus, we analysed the brain contents of N-arachidonoylethanolamine (anandamide, AEA), the first discovered endocannabinoid, in rats subjected to daily injections of increasing doses of morphine, according to a schedule designed to render the animals opiate-dependent. Although evidence of physical dependence was assured by the appearance of somatic and neurovegetative responses in these animals after an acute challenge with naloxone, there were no changes in the contents of this endocannabinoid in any of the brain regions analysed. By contrast, we observed a significant decrease in the specific binding for CB(1) receptors in the midbrain and the cerebral cortex of morphine-dependent rats, with no changes in the other regions. The decrease in the cerebral cortex was, however, accompanied by a rise in the activation of signalling mechanisms by CB(1) receptor agonists, as revealed by WIN-55,212-2-stimulated [(35)S]GTPgammaS binding, whereas a reduction in this parameter was measured in the brainstem of morphine-dependent rats. In summary, the present data are indicative of the existence of an alteration of the endocannabinoid transmission during morphine dependence in rats, although the changes observed were region-dependent and affected exclusively CB(1) receptors with no changes in endocannabinoid levels. Because the changes occurred in regions of the midbrain, the cerebral cortex and the brainstem, which have been implicated in drug dependence, our data suggest that pharmacological manipulation of the endocannabinoid system might be a novel tool to reduce morphine addiction.
- Subjects
DRUG abuse; MORPHINE; NALOXONE; CEREBRAL cortex; AMIDES; ANALGESICS; ANIMAL experimentation; ARACHIDONIC acid; BASAL ganglia; BINDING sites; BRAIN stem; CELL receptors; CELLULAR signal transduction; COMPARATIVE studies; DRUG receptors; DRUGS; DRUG administration; HETEROCYCLIC compounds; HYDROCARBONS; INTRAVENOUS injections; RESEARCH methodology; MEDICAL cooperation; NARCOTICS; NEURAL transmission; NEUROTRANSMITTERS; RATS; REINFORCEMENT (Psychology); RESEARCH; SUBSTANCE abuse; EVALUATION research
- Publication
Addiction Biology, 2003, Vol 8, Issue 2, p159
- ISSN
1355-6215
- Publication type
journal article
- DOI
10.1080/1355621031000117383