Cannabinoid–serotonin interactions in alcohol‐preferring vs. alcohol‐avoiding mice

Abstract

Because cannabinoid and serotonin (5-HT) systems have been proposed to play an important role in drug craving, we investigated whether cannabinoid 1 (CB1) and 5-HT 1A receptor ligands could affect voluntary alcohol intake in two mouse strains, C57BL/6 J and DBA/2 J, with marked differences in native alcohol preference. When offered progressively (3-10% ethanol) in drinking water, in a free-choice procedure, alcohol intake was markedly lower ( 70%) in DBA/2 J than in C57BL/6 J mice. In DBA/2 J mice, chronic treatment with the cannabinoid receptor agonist WIN 55,212-2 increased alcohol intake. WIN 55,212-2 effect was prevented by concomitant, chronic CB1 receptor blockade by rimonabant or chronic 5-HT 1A receptor stimulation by 8-hydroxy-2-(di-n-propylamino)-tetralin, which, on their own, did not affect alcohol intake. In C57BL/6 J mice, chronic treatment with WIN 55,212-2 had no effect but chronic CB1 receptor blockade or chronic 5-HT 1A receptor stimulation significantly decreased alcohol intake. Parallel autoradiographic investigations showed that chronic treatment with WIN 55,212-2 significantly decreased 5-HT 1A -mediated [35 S]guanosine triphosphate-c-S binding in the hippocampus of both mouse strains. Conversely, chronic rimonabant increased this binding in C57BL/6 J mice. These results show that cannabinoid neurotransmission can exert a permissive control on alcohol intake, possibly through CB1-5-HT 1A interactions. However, the differences between C57BL/6 J and DBA/2 J mice indicate that such modulations of alcohol intake are under genetic control.

Reflection impulsivity in adolescent cannabis users: a comparison with alcohol-using and non-substance-using adolescents

“…The serotonergic system has been implicated in the regulation of impulse control, behavioural inhibition and effective decision making (Evenden 1999b;Clark et al 2004;Soubrié 1986), with reductions in serotonin (5-hydroxytryptamine, 5-HT) levels being associated with reduced inhibitory control and increases in impulsive behaviour (Clark et al 2009;Evenden 1999b). Cannabinoids have been shown to interact with 5-HT receptors (Kelaï et al 2006;Kimura et al 1998) and evidence from preclinical studies suggests the involvement of cannabinoid receptors (CB1) in the regulation of serotonergic responses (Lau and Schloss 2008;Mato et al 2007), whereby stimulation of CB1 receptors reduces (Balazsa et al 2008) and inhibits (Best and Regehr 2008;Nakazi et al 2000) 5-HT release. Administration of THC has been shown to decrease serotonergic activity in various brain regions in animal studies (Molina-Holgado et al 1993;Moranta et al 2004;Sagredo et al 2006).…”

Effects of chronic treatment with citalopram on cannabinoid and opioid receptor-mediated G-protein coupling in discrete rat brain regions

“…Serotonincannabinoid interactions play a role in genetically based alcohol preference in mice (Kelai et al 2006). The CB 1 antagonist SR141716A has been shown to increase monoaminergic neurotransmission in the frontal cortex (Tzavara et al 2003), an area associated with decreased serotonergic function in depression.…”

Role of the Endocannabinoid System in Alcohol-Related Behaviors

“…Interestingly, the prefrontal cortex (PFC) appears to play a critical role in regulating the alcohol drinking behavior as revealed by a dose dependent suppression of alcohol self-administration in alcohol preferring rats when rimonabant was given locally into the PFC [82]. Conversely, the CB1 receptor stimulation is shown to enhance alcohol drinking behavior in both alcohol preferring and alcohol non-preferring rodents [55,61,84,104]. In addition, an increased motivation to drink more beer in rats following administration of the CB1 receptor agonist (CP-55, 940) and complete abolition of this effect after treatment with rimonabant has also been shown [83].…”

“…Manipulation of CB1 receptor function on voluntary alcohol consumption: Recent reports provide evidence for a direct linkage between CB1 receptor function and alcohol consumption [53,54,[75][76][77][78][79][80][81][82][83][84][85][86][87][88][89] (Table 1). For instance, the administration of SR141716A (rimonabant) reduces alcohol consumption in rodent models [54,[75][76][77][78][79][80][81][82] (Fig.…”

“…In this regard, generation of CB1 receptor null mutant mice has provided several insights into the role of CB1 receptor in physiology and behavior. It has been demonstrated that mice lacking CB1 receptor gene with two different genetic background (C57BL/6J and CD1) consume less alcohol [ 54,55,[84][85][86][87][88][89] (Fig. 1) and exhibit reduced effect on alcohol-induced DA release in the nucleus accumbens (NAc) compared to their WT controls [85].…”