Cannabinoid receptor modulation changes the accumbal neuronal responses to morphine in the reinstatement of morphine-induced conditioned place preference.

The nucleus accumbens (NAc) is a central component of the brain reward system. It has been known that most of the drugs of abuse such as opioids and cannabinoids affect the NAc. Although cannabinoids can modulate different stages of morphine encounter such as the reinstatement of morphine-induced conditioned place preference (CPP), there is no evidence for the NAc neurons' response to prove it. That is why the present study was designed. The procedure was as follows: The rats were entered to CPP by sc 5 mg/kg morphine in three consecutive days. During the extinction period or in the reinstatement phase, icv WIN 55,212-2 (10mM/5 μL dimethyl sulfoxide [DMSO] 10%) or AM251 (0.5mM/5-μL DMSO 10%) was infused in separate groups. Also, the NAc neurons' response to cannabinoid modulation in reinstatement to morphine was investigated by extracellular single unit recording. As a result, the cannabinoid in the reinstatement phase decreased the NAc neuronal activity. The CB1 receptor inhibition during the extinction period increased the NAc firing rate after ip 1 mg/kg morphine. Also, the inhibition of this receptor in the reinstatement phase increased the NAc neurons' firing rate. The inhibitory effect of cannabinoid on the NAc neuronal activity in the reinstatement has indicated the possible potency of cannabinoid to induce reinstatement of morphine-induced CPP alone and in the absence of a priming dose of morphine. Also, the different effects of the CB1 agonist during the extinction period in the reinstatement phase suggest different mechanisms underlying these two parts.