Cannabinoid receptors in the basolateral amygdala are involved in the potentiation of morphine rewarding properties in the acquisition, but not expression of conditioned place preference in rats

• Intra-BLA cannabinoid agonist alone could induce place preference in rats.
• Intra-BLA cannabinoid agonist could potentiate morphine-induced place preference.
• Microinjection of AM251 alone in the BLA could induce conditioning place aversion.
• Blockade of CB1 receptors in the BLA reduced morphine conditioned place preference.

Several studies show the role of the basolateral amygdala (BLA) in drug-seeking, relapse and the brain׳s emotional systems. Several lines of evidence indicate a functional interaction between opioid and endogenous cannabinoid systems. In the present study, we investigated the role of intra-BLA cannabinoid CB1 receptors in the potentiation, acquisition and expression of morphine-induced conditioned place preference (CPP). One-hundred and forty-two adult male Wistar rats weighing 230–280 g were bilaterally implanted by two separate cannulae into the BLA. The CPP paradigm was done, and conditioning score and locomotor activity were recorded by Ethovision software. Results showed that intra-BLA administration of different doses of WIN55,212-2 (1, 2 and 4 mmol/0.3 µl DMSO) as a cannabinoid receptor agonist during the conditioning phase induced place preference in animals that received the ineffective (2 mg/kg) dose of morphine compared to respective control group in saline-treated animals. On the other hand, intra-BLA injection of the cannabinoid CB1 receptor antagonist AM251 (45 and 90 µmol/0.3 µl DMSO) during the 3-day conditioning phase reduced morphine-induced CPP. Furthermore, microinjection of both AM251 (15, 45 and 90 µmol) and WIN55,212-2 (1–4 mmol), into the BLA had no effect on the expression of morphine (5 mg/kg)-induced CPP. Our findings suggest that cannabinoid CB1 receptors in the BLA are involved in the development of reward-related behaviors and they can potentiate the rewarding effects of morphine. It seems that the glutamatergic projection from the BLA to the nucleus accumbens and reward-related learning in the hippocampus may be involved in the acquisition and expression of opioid reward-related behaviors in rats.