Dopaminergic augmentation of delta-9-tetrahydrocannabinol (THC) discrimination: possible involvement of D(2)-induced formation of anandamide.
Marcello Solinas, Gianluigi Tanda, Carrie E Wertheim, Steven R Goldberg
Psychopharmacology April 2010 DOI: 10.1007/s00213-010-1789-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats trained to discriminate THC from vehicle |
| Interventions | THC Cocaine Amphetamine SKF-38393 Quinpirole Apomorphine SCH-23390 Raclopride Rimonabant |
| Dose | 3 mg/kg THC |
| Topics | Cannabis |
| Key findings | Dopamine agonists did not substitute for THC, but D2 (not D1) agonists and indirect agonists augmented THC discrimination; dopamine antagonists did not reduce THC discrimination. The augmentation likely involves D2-induced anandamide release, as rimonabant blocked it and FAAH inhibition enhanced it. |
Abstract
Although delta-9-tetreahydrocannabinol (THC)-induced elevations in accumbal dopamine levels are believed to play an important role in the abuse-related effects of cannabis, little direct evidence has been provided that the dopaminergic system is involved in the psychotropic effects of THC. The objective of this study is to investigate whether drugs activating or blocking the dopaminergic system modulate the discriminative effects of THC. In rats that had learned to discriminate 3 mg/kg of THC from vehicle injections, the indirect dopaminergic agonists cocaine and amphetamine, the D(1)-receptor agonist SKF-38393, and the D(2)-receptor agonists quinpirole and apomorphine did not produce significant THC-like discriminative effects. However, both cocaine and amphetamine and D(2)-, but not the D(1)-, receptor agonists, augmented THC discrimination. Neither the D(1)-receptor antagonist SCH-23390 nor the D(2)-receptor antagonist raclopride reduced the discriminative effects of THC, even at doses that significantly depressed baseline operant responding. However, the D(2)-, but not the D(1)-, antagonist counteracted the augmentation of THC's discriminative effects produced by cocaine and amphetamine. We hypothesized that release of anandamide by activation of D(2) receptors was responsible for the observed augmentation of THC discrimination. This hypothesis was supported by two findings. First, the cannabinoid CB(1)-receptor antagonist rimonabant blocked quinpirole-induced augmentation of THC discrimination. Second, inhibition of anandamide degradation by blockade of fatty acid amide hydrolase augmented the THC-like effects of quinpirole. Dopamine does not play a major role in THC discrimination. However, activation of the dopaminergic system positively modulates the discriminative effects of THC, possibly through D(2)-induced elevations in brain levels of anandamide.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 2
Cites 10
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