Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat: interaction with the opioid system

The effect of CP 55,940 {(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl] -trans-4-(3-hydroxypropyl)cyclo-hesanol}, heroin and etonitazene on intrace rebroventricular (i.c.v.) self-administration in a free-choice procedure wa s evaluated in rats. Animals were trained in 1-h daily sessions with a cont inuous reinforcement schedule to press two active levers to obtain the vehi cle of each drug. Then, when a stable baseline was reached, each drug could be self-administered by pressing the lever found to be less preferred duri ng training, while the vehicle came from the other. The number of bar press ings associated with the delivery of increasing unit doses of CP 55,940 (0. 1, 0.2, 0.4, 0.8, 1.6 mug/2 mul/infusion), heroin (0.125, 0.25, 0.5, 1, 2 m ug/2 mul/infusion) or etonitazene (0.1-0.2-0.5-1 mug/2 mul/infusion) and wi th the delivery of the corresponding vehicle was fitted by symmetrical para bolas. The mean drug intake was linearly related to the log of self-adminis tered drugs. Pretreatment with SR141716A [N-piperidino-5-(4-chlorophenyl)1- (2,4-dichloro-phenyl)-4-methylpyrazole-3-carboxamide] (0.5 mg/kg) or naloxo ne HCl (2 mg/kg/i.p.) 15 min before each daily session reduced the self-adm inistration of both CP 55,940 and heroin. The combination of CP 55,940 with heroin or etonitazene reduced the number of drug-associated lever pressing s compared to that obtained with the maximal reinforcing unit dose of each drug alone. These findings suggest there may be a strong interaction betwee n opioids and the cannabinoid system. (C) 2001 Elsevier Science B.V. All ri ghts reserved.