Effect of physical stress on the alteration of mesolimbic system apoptotic factors in conditioned place preference paradigm.

Mesocorticolimbic (MCL) dopaminergic system has an essential role in the rewarding action of opiates and is proved to be influenced by stress. Additionally, both morphine and stress can induce apoptosis. In this study, we investigated the effects of morphine-induced conditioned place preference (CPP) in the presence and absence of stress on the changes of apoptotic factors (Bax/Bcl-2 ratio, caspase-3 activation and PARP degradation) in the MCL system. Male Wistar rats were divided into two saline- and morphine-treated supergroups, each of which consisted of control, acute stress (AS) and subchronic stress (SS) subgroups. In all groups, the CPP paradigm was performed; thereinafter alternations of apoptotic factors in the nucleus accumbens, amygdala, striatum and prefrontal cortex were measured. The results indicated that in the saline-treated animals, AS and SS increased apoptotic factors significantly in the mentioned areas (except for the Bax/Bcl-2 ratio after AS in the Str). In addition, in these animals, conditioning scores decreased after SS but not after AS. In the morphine-treated animals, AS and SS increased apoptotic factors remarkably (except for the Bax/Bcl-2 ratio after AS and SS in the Str and caspase-3 activation after AS in the NAc) and also decreased conditioning scores. Our findings suggest that in the saline- or morphine-treated animals, AS and SS can increase the apoptotic factors in the MCL system and it is more prominent in the morphine-treated animals.