Cannabinoid modulation of opiate reinforcement through the ventral striatopallidal pathway.
Neuropsychopharmacol. 2005-08-03; 31(4): 804-813
DOI: 10.1038/sj.npp.1300848
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1. Neuropsychopharmacology. 2006 Apr;31(4):804-13.
Cannabinoid modulation of opiate reinforcement through the ventral
striatopallidal pathway.
Caillé S(1), Parsons LH.
Author information:
(1)Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA
92037, USA.
Recent evidence indicates that cannabinoid-1 (CB1) receptors play a role in the
mediation of opiate reward, though the neural mechanisms for this process have
not been characterized. The present experiments investigated the influence of CB1
receptors in the ventral striatopallidal system on opiate-induced neurochemical
events and opiate self-administration behavior in rats. Acute morphine
administration (3 mg/kg) significantly reduced ventral pallidal GABA efflux in a
manner similar to that produced by heroin self-administration. This neurochemical
effect was reversed by doses of the selective CB1 antagonist SR 141716A
(Rimonabant; 1 and 3 mg/kg) that also significantly reduce opiate reward.
Morphine-induced increases in nucleus accumbens dopamine levels were unaltered by
SR 141716A. Intravenous heroin self-administration (0.02 mg/infusion) was
significantly reduced by intra-accumbens, but not intraventral pallidal SR
141716A infusions (1 and 3 microg/side), implicating nucleus accumbens CB1
receptors in the modulation of opiate reinforcement. In contrast, SR14716A did
not alter cocaine self-administration (0.125 mg/inf), cocaine-induced (10 mg/kg)
decrements in ventral pallidal GABA efflux or cocaine-induced increases in
accumbens dopamine. This is consistent with evidence that selective inactivation
of CB1 receptors reduces opiate-, but not psychostimulant-maintained
self-administration. The CB1 receptor agonist WIN 55,212-2 (5 mg/kg) reduced
pallidal GABA efflux in a manner similar to morphine, and this effect was
reversed by the opiate receptor antagonist naloxone. Collectively these findings
suggest that CB1 receptors modulate opiate reward through the ventral
striatopallidal projection and that the modulation of this projection system may
be involved in the reciprocal behavioral effects between cannabinoids, and
opioids.
DOI: 10.1038/sj.npp.1300848
PMID: 16123766 [Indexed for MEDLINE]