Involvement of central cannabinoid (CB 1 ) receptors in the establishment of place conditioning in rats

Abstract

The involvement of cannabinoid processes in positive reinforcement was studied using an unbiased, one-compartment, conditioned place preference (CPP) procedure in rats. This was achieved by examining the ability of the selective antagonist of the CB1 cannabinoid receptor subtype, SR 141716, to counteract the CPP supported by classical reinforcers. The acquisition of CPP induced by cocaine (2 mg/kg), morphine (4 mg/kg) and food (standard chow and sucrose pellets) was dose-dependently blocked by pre-pairing administration of SR 141716 (0.03-3 mg/kg). However, SR 141716 (up to 10 mg/kg) did not significantly counteract the expression of cocaine-induced CPP. On the other hand, the synthetic CB receptor agonist, WIN 55212-2 (0.3-1 mg/kg), established a robust place aversion (CPA), as already described with other agonists, and CPP was never observed, even at 100-fold lower doses. The aversive effect of WIN 55212-2 was reversed by SR 141716 (0.3-1 mg/kg), suggesting that it was accounted for by the stimulation of CB1 receptors. These findings indicate that, on their own, CB receptor agonists are unable to generate the processes necessary to induce a pleasurable state in animals, as assessed in place conditioning procedures. Nevertheless, a cannabinoid link may be involved in the neurobiological events, allowing the perception of the rewarding value of various kinds of reinforcers. However, a permanent endogenous cannabinoid tone seems unlikely to be necessary to ensure the organism a basal hedonic level since, given alone, SR 141716 supported neither CPP nor CPA.

Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ9-tetrahydrocannabinol

“…Previous reports have found that lower doses of THC are not effective as conditioning stimuli in place conditioning procedures (Mallet and Beninger, 1998;Parker and Gillies, 1995;Robinson et al, 2003). In contrast, higher doses of cannabinoids such as CP 55,940 (McGregor et al, 1996), WIN 55212-2 (Chaperon et al, 1998), THC (Sanudo-Pena et al, 1997); (Cheer et al, 2000); (Hutcheson et al, 1998); (Parker and Gillies, 1995), and HU210 (Cheer et al, 2000) produced aversion in place conditioning procedures in both rats and mice. Further, the aversive effects produced by THC were blocked by the cannabinoid receptor antagonist, SR141716A (Chaperon et al, 1998), suggesting that these effects were CB1 receptor-mediated.…”

“…In contrast, higher doses of cannabinoids such as CP 55,940 (McGregor et al, 1996), WIN 55212-2 (Chaperon et al, 1998), THC (Sanudo-Pena et al, 1997); (Cheer et al, 2000); (Hutcheson et al, 1998); (Parker and Gillies, 1995), and HU210 (Cheer et al, 2000) produced aversion in place conditioning procedures in both rats and mice. Further, the aversive effects produced by THC were blocked by the cannabinoid receptor antagonist, SR141716A (Chaperon et al, 1998), suggesting that these effects were CB1 receptor-mediated. Taken together, across strains and species, most studies have reported that cannabinoids produce conditioned place aversion rather than conditioned place preference.…”

Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

“…Pretreatment with the cannabinoid CB 1 receptor antagonist rimonabant (SR141716; Rinaldi-Carmona et al, 1994) reduced nicotine, ethanol, methamphetamine, and morphine self-administration in rodents (Arnone et al, 1997;Navarro et al, 2001;Cohen et al, 2002;Vinklerova et al, 2002). Rimonabant also blocked the acquisition of conditioned place preference induced by morphine and cocaine (Chaperon et al, 1998). Although rimonabant was reported not to reduce cocaine self-administration, it prevented cocaine relapse induced by cocaine and by cocaine-associated cues in rats (De Vries et al, 2001).…”

A Critical Interaction between Dopamine D2 Receptors and Endocannabinoids Mediates the Effects of Cocaine on Striatal GABAergic Transmission

“…The involvement of endocannabinoids in drug addiction is likely to reflect the effects of these compounds in the so-called 'reward circuitry', which includes midbrain DA neurons and their target structures (Berke and Hyman, 2000;Everitt and Wolf, 2002;Maldonado and Rodriguez de Fonseca, 2002). With respect to the role of endocannabinoids in opiate addiction, it has been reported that the rewarding effects of morphine are blocked by both pharmacological (Chaperon et al, 1998) and genetic inactivation of cannabinoid CB1 receptors (Martin et al, 2000), while blockade of CB1 receptors abolishes morphine intravenous self-administration (Ledent et al, 1999), and precipitates withdrawal symptoms in morphine-dependent rats (Navarro et al, 1998).…”