Pharmacological activation of CB1 and D2 receptors in rats: predominant role of CB1 in the increase of alcohol relapse

Abstract

The classical dopamine D2 receptor has been widely studied in alcoholism. Recently, different studies have explored the role of the CB1 receptor in alcohol-related behavior. In alcohol addiction, relapse is one of the central features. In light of this, we investigated the functional roles of and interactions between CB1 and D2 receptors in alcohol relapse. We used the learned task of alcohol operant self-administration in Wistar rats. In order to evaluate alcohol relapse, we set up a protocol essentially based on the alcohol deprivation effect. We found that subchronic activation of CB1 (WIN 55,212-2, 2 mg/kg), but not D2 receptors (quinpirole, 1 mg/kg), during a period of alcohol deprivation increased long-lasting alcohol relapse. The cannabinoid-induced potentiation of alcohol relapse was mediated by a motivational and appetitive component, and not merely by alcohol consumption. This potentiation was prevented by the pharmacological inactivation of D2 receptors (raclopride, 0.1-0.3 mg/kg). Together, these results essentially demonstrate that activation of CB1 receptors plays a key role in the increase of alcohol relapse, whereas inactivation of D2 receptors modulates this aberrant behavior. We suggest that there exists a functional and interactive relationship between both receptor systems, which controls alcohol relapse and alcohol-learned tasks.

Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption

“…In our experimental model this downregulation occurs in the absence of DRD2, which suggests that the dopaminergic system affects the interaction between ethanol and the endocannabinoid system. Similarly, Alen et al (2008) showed that pharmacological inactivation of DRD2 prevents cannabinoid-induced alcohol relapse. These results are in agreement with the hypothesis that DRD2-mediated neurotransmission is critical for ethanol-related neuronal signaling and suggest that a functional interaction between ethanol and the dopaminergic and endocannabinoid systems exists in the mammalian brain.…”

Involvement of Dopamine D2 Receptors in Addictive-Like Behaviour for Acetaldehyde

“…Remarkably, some of the behavioural features of orally self-administered ACD are sensitive to the pharmacological modulation of the cannabinoid CB1 receptor [17], as well as of the opioid neurotransmission [42]. These systems are largely involved in the induction of alcohol drinking behaviour and relapse [59], [60], [35] and can likely influence ACD drinking behaviour through the modulation of the DAergic reward pathway, thus causing DA release in the nucleus accumbens [61].…”

Functional Interactions between Endogenous Cannabinoid and Opioid Systems: Focus on Alcohol, Genetics and Drug-Addicted Behaviors

“…Due to the recent increase in the literature regarding CB1 receptors as a pharmacological target for the treatment of alcoholism, there have been several extensive reviews published [209][210][211]. Based on these studies and recent findings from our own group [212], it is plausible to conclude that the endocannabinoid system mediates not only alcohol intake but the motivational and emotional properties of alcohol intake, seeking and craving.…”