Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain cannabinoid CB 1 receptor binding and mRNA levels

Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain... Recent evidence suggest that the endocannabinoid system might be a component of the brain reward system and, then, play a role, not only in cannabinoid tolerance/dependence, but also in dependence/withdrawal to other drugs of abuse. However, there are not many studies that compare the changes in endocannabinoid ligands and/or receptors in brain regions (particularly in those areas related to reinforcement processes) during dependence to opiates, cocaine or alcohol. The present study addressed this objective, by examining the changes in CB 1 receptor binding (measured by ( 3 H)-CP55,940 autoradiography) and its mRNA levels (measured by in situ hybridization) in different brain regions of animals chronically exposed to morphine, cocaine or ethanol. The results showed that these three drugs produced different changes in CB 1 receptor binding and mRNA levels, a finding that precludes the existence of a common alteration of the endocannabinoid system during dependence states to these habit-foming drugs. Thus, chronic ethanol exposure was usually uneffective in altering both CB 1 receptor binding and mRNA levels in all regions examined. In contrast, chronic cocaine exposure produced significant changes only at the level of CB 1 receptor mRNA, with decreases of the transcript levels in the ventromedial hypothalamic nucleus and the superficial and deep layers of the cerebral cortex, but no changes in the hippocampal, motor and limbic structures. Finally, chronic morphine exposure increased the density of CB 1 receptors in the medial caudate-putamen, but decreased their mRNA levels in this region and also in the lateral caudate-putamen and the cerebellum. In limbic structures, chronic morphine exposure increased both binding and mRNA levels for CB 1 receptors in the septum nuclei. Binding was also increased in the nucleus accumbens, but reduced in the basolateral amygdala. In hippocampal structures, chronic morphine exposure reduced CB 1 receptor binding in the dentate gyrus, although mRNA levels were unaffected in this region, but increased in the CA2 subfield of the Ammon's horn. The results indicate that mechanisms of dependence for alcohol, cocaine and morphine are different in terms of their impact on the endocannabinoid system. Alcohol did not produce any effects on CB 1 receptor binding and mRNA levels, whereas cocaine only affected transcript levels in selected regions and morphine produced divergent and region-dependent effects. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug and Alcohol Dependence Elsevier

Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain cannabinoid CB 1 receptor binding and mRNA levels

Loading next page...
 
/lp/elsevier/chronic-exposure-to-morphine-cocaine-or-ethanol-in-rats-produced-PemhKxjMV0
Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Science Ireland Ltd
ISSN
0376-8716
D.O.I.
10.1016/S0376-8716(01)00186-7
Publisher site
See Article on Publisher Site

Abstract

Recent evidence suggest that the endocannabinoid system might be a component of the brain reward system and, then, play a role, not only in cannabinoid tolerance/dependence, but also in dependence/withdrawal to other drugs of abuse. However, there are not many studies that compare the changes in endocannabinoid ligands and/or receptors in brain regions (particularly in those areas related to reinforcement processes) during dependence to opiates, cocaine or alcohol. The present study addressed this objective, by examining the changes in CB 1 receptor binding (measured by ( 3 H)-CP55,940 autoradiography) and its mRNA levels (measured by in situ hybridization) in different brain regions of animals chronically exposed to morphine, cocaine or ethanol. The results showed that these three drugs produced different changes in CB 1 receptor binding and mRNA levels, a finding that precludes the existence of a common alteration of the endocannabinoid system during dependence states to these habit-foming drugs. Thus, chronic ethanol exposure was usually uneffective in altering both CB 1 receptor binding and mRNA levels in all regions examined. In contrast, chronic cocaine exposure produced significant changes only at the level of CB 1 receptor mRNA, with decreases of the transcript levels in the ventromedial hypothalamic nucleus and the superficial and deep layers of the cerebral cortex, but no changes in the hippocampal, motor and limbic structures. Finally, chronic morphine exposure increased the density of CB 1 receptors in the medial caudate-putamen, but decreased their mRNA levels in this region and also in the lateral caudate-putamen and the cerebellum. In limbic structures, chronic morphine exposure increased both binding and mRNA levels for CB 1 receptors in the septum nuclei. Binding was also increased in the nucleus accumbens, but reduced in the basolateral amygdala. In hippocampal structures, chronic morphine exposure reduced CB 1 receptor binding in the dentate gyrus, although mRNA levels were unaffected in this region, but increased in the CA2 subfield of the Ammon's horn. The results indicate that mechanisms of dependence for alcohol, cocaine and morphine are different in terms of their impact on the endocannabinoid system. Alcohol did not produce any effects on CB 1 receptor binding and mRNA levels, whereas cocaine only affected transcript levels in selected regions and morphine produced divergent and region-dependent effects.

Journal

Drug and Alcohol DependenceElsevier

Published: Mar 1, 2002

References

  • Cannabinoid transmission and reward-related events
    Gardner, E.L.; Vorel, S.R.
  • Lack of morphine-induced dopamine release in the nucleus accumbens of cannabinoid CB 1 receptor knockout mice
    Mascia, M.S.; Obinu, M.C.; Ledent, C.; Parmentier, M.; Böhme, G.A.; Imperato, A.; Fratta, W.
  • Anandamide decreases naloxone-precipitated withdrawal signs in mice chronically treated with morphine
    Vela, G.; Ruiz-Gayo, M.; Fuentes, J.A.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off