Intra-accumbal CB1 receptor blockade reduced extinction and reinstatement of morphine.

The limbic dopaminergic reward system is the main target of morphine-like drugs which begins from the ventral tegmental area (VTA) and sends its dopaminergic projections to the nucleus accumbens (NAc), amygdala, hippocampus and prefrontal cortex. Cannabinoid receptors exist in afferent neurons from these areas to the NAc and can modulate glutamate synaptic transmission in the NAc. Cannabinoids can interact with the opiate system in reward-related behaviors; nevertheless it has not been shown theses systems interaction in extinction duration and reinstatement. In the present study, the effects of bilateral intra-accumbal administration of AM251, a CB1 receptor antagonist, on the duration of extinction phase and reinstatement to morphine were investigated by conditioned place preference (CPP) paradigm. Forty eight adult male albino Wistar rats were used. Bilateral intra-accumbal administration of AM251 (15, 45 and 90 μM/0.5 μl DMSO per side) were performed. Subcutaneous administration of morphine (5 mg/kg) in three consecutive days was used to induce CPP. The results showed that administration of maximal dose of AM251 during extinction period significantly reduces duration of the extinction and reinstatement to morphine. Administration of the middle dose during extinction period significantly attenuated reinstatement to morphine. Single microinjection of the middle dose just before reinstatement phase significantly attenuated reinstatement to morphine only, while bilateral intra-accumbal administration of neither the lowest dose nor the vehicle (DMSO) had any effects. These results for the first time indicated that CB1 receptors within the NAc are involved in the maintenance of morphine rewarding properties, and morphine seeking behaviors in extinguished morphine-induced CPP rats.
Copyright © 2015. Published by Elsevier Inc.