Title |
Opposing roles of CB1 and CB2 cannabinoid receptors in the stimulant and rewarding effects of cocaine
|
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Published in |
British Journal of Pharmacology, September 2018
|
DOI | 10.1111/bph.14473 |
Pubmed ID | |
Authors |
Pedro H Gobira, Ana C Oliveira, Julia S Gomes, Vivian T da Silveira, Laila Asth, Juliana R Bastos, Edleusa M Batista, Ana C Issy, Bright N Okine, Antonio C de Oliveira, Fabiola M Ribeiro, Elaine A Del Bel, Daniele C Aguiar, David P Finn, Fabricio A Moreira |
Abstract |
The endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) bind to CB1 and CB2 receptors in the brain and modulate the mesolimbic dopaminergic pathway. This neurocircuitry is engaged by psychostimulant drugs, including cocaine. Although it is known that CB1 antagonism as well as CB2 activation inhibit certain effects of cocaine, they have been investigated separately. Here we tested the hypothesis that there is a reciprocal interaction between CB1 blockade and CB2 activation in modulating behavioural responses to cocaine. Male Swiss mice received intraperitoneal injections of cannabinoid-related drugs followed by cocaine. The animals were tested for cocaine-induced hyperlocomotion, c-Fos expression in the nucleus accumbens and conditioned place preference. The levels of endocannabinoids after cocaine injections were also analysed. The CB1 antagonist, rimonabant, and the CB2 agonist, JWH133, prevented cocaine-induced hyperlocomotion. The same result as obtained by combining sub-effective doses of both compounds. The CB2 receptor antagonist, AM630, reversed the inhibitory effects of rimonabant in cocaine-induced hyperlocomotion and c-Fos expression in the nucleus accumbens. Selective inhibitors of anandamide and 2-AG hydrolyses (URB597 and JZL184, respectively) failed to modify this response. However, JZL184 did prevent cocaine-induced hyperlocomotion if administered after a sub-effective dose of rimonabant. Cocaine did not change brain endocannabinoid levels. Finally, CB2 blockade reversed the inhibitory effect of rimonabant in the acquisition of cocaine-induced conditioned place preference. The present data support the hypothesis that CB1 and CB2 receptors work in concert with opposing functions to modulate certain addiction-related effects of cocaine. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 3 | 75% |
Colombia | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 75% |
Scientists | 1 | 25% |
Mendeley readers
Geographical breakdown
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Unknown | 59 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 10 | 17% |
Student > Master | 9 | 15% |
Student > Bachelor | 7 | 12% |
Professor | 4 | 7% |
Student > Doctoral Student | 4 | 7% |
Other | 12 | 20% |
Unknown | 13 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 10 | 17% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 14% |
Agricultural and Biological Sciences | 5 | 8% |
Medicine and Dentistry | 5 | 8% |
Biochemistry, Genetics and Molecular Biology | 4 | 7% |
Other | 9 | 15% |
Unknown | 18 | 31% |