Conditioned place preference induced by the cannabinoid agonist CP 55,940:Interaction with the opioid system

Cannabinoids appear atypical as drugs of abuse since controversial data exi st concerning the ability to lower the thresholds for electrical self-stimu lation (Stark and Dews, 1980; Gardner et al., 1988; Gardner, 1992) and to s upport self-administration (Martellotta et al., 1998; Tanda et al., 2000) o r conditioned place preference in animals (Lepore et al., 1995; Parker and Gillies, 1995; McGregor et al., 1996; Sanudo-Pena et al., 1997; Chaperon et al., 1998; Hutcheson et al., 1998; Mallet and Beninger, 1998; Cheer et al. , 2000; Valjent and Maldonado, 2000). Opioids and cannabinoids share some p harmacological properties (Manzanares et al., 1999). The most interactions were found in antinociception (Welch and Stevens, 1992; Smith et al., 1994) and, to a lesser extent, in drug reinforcement (Chen et al., 1990; Vela et al., 1995; Tanda et al., 1997). In the present study we asked whether: (1) a potent synthetic cannabinoid receptor agonist, [(-)-cis-3-[2-hydroxy-4-( 1,1-dimethylheptil)-phenyl]-trans-4-(3-hydroxy propyl) cyclohexanol] (CP 55 ,940) (from 10 to 40 mug/kg), which binds to the brain cannabinoid receptor s with high affinity (Herkenham et al., 1991), would induce conditioned pla ce preference, in comparison with heroin (from 0.1 to 5 mg/kg); (2) what ty pe of receptor was involved; (3) what kind of interaction there was between the two drugs, when given in combination, on reward. CP 55,940 elicited a conditioned place preference only at a dose of 20 mug/kg similar in intensi ty to that of heroin (2 mg/kg). The reinforcing properties of the cannabino id agonist were fully antagonised by pretreatment with the brain cannabinoi d receptor-1 (CB1) antagonist, [N-piperidino-5-(4-chlorophenyl) 1-(2,4-dich loro-phenyl)-4-methyl pyrazole-3-carboxamide hydrochloride] (SR 141716A) an d naloxone. The combination of CP 55,940 and heroin, at the reinforcing dos es, led to a reward which did not show any additive effect. Taken together these findings are important for understanding how the cannabinoids produce reward and the interconnection of the opioid and cannabinoid system in the motivation. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights r eserved.