Microinjection of WIN55,212-2 as a Cannabinoid Agonist into the Basolateral Amygdala Induces Sensitization to Morphine in Rats

Introduction: Previous studies have shown that the basolateral amygdale (BLA) is rich of CB1 cannabinoid receptors and involved in cannabinoid-induced antinociception. Also, it seems that there are functional interactions between the cannabinoid CB1 and opioid receptors in the process of sensitization to opiates. In the present study, we tried to examine the role of intra-BLA cannabinoid receptors on development of sensitization to morphine.  Methods: In this study, seventy two adult male albino Wistar rats weighting 230-280 g were included. Antinociception response of subcutaneous (sc), administration of saline (1 ml/kg), and morphine (1 and 10 mg/kg) were measured by the tail-flick test in animals that were received subcutaneous administration of morphine (5 mg/kg) or saline (1 ml/kg) once a day for three days (sensitization period), followed by five days free of drug. The dose of 1 mg/kg of morphine was selected as the appropriate (ineffective) dose in the next stages of experiment for measuring analgesia in the tail-flick test in sensitive animals which previously received bilateral intra-BLA CB1 receptor agonist, WIN55,212-2 (0.5, 1, 2 and 4 mM/0.3 μl/side), DMSO, or saline (0.3 μl/side) during sensitization period.  Results: Bilateral intra-BLA administration of WIN55, 212-2, increased morphine-induced antinociception in ineffective dose, while this effect was not observed in the groups that received DMSO or saline. Our findings indicated that CB1 receptors within the BLA are involved in the sensitization to morphine.  Discussion: It seems that glutamatergic projections from the BLA to the nucleus accumbens are involved in the development of morphine sensitization induced by cannabinoids.