Effect of circadian rhythm disturbance on morphine preference and addiction in male rats: Involvement of period genes and dopamine D1 receptor.

It is claimed that a correlation exists between disturbance of circadian rhythms by factors such as alteration of normal light-dark cycle and the development of addiction. However, the exact mechanisms involved in this relationship are not much understood. Here we have studied the effect of constant light on morphine voluntary consumption and withdrawal symptoms and also investigated the involvement of Per1, Per2 and dopamine D1 receptor in these processes. Male wistar rats were kept under standard (LD) or constant light (LL) conditions for one month. The plasma concentration of melatonin was evaluated by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was used to determine the mRNA expression of Per1, Per2 and dopamine D1 receptor in the striatum and prefrontal cortex. Morphine preference (50mg/L) was evaluated in a two-bottle-choice paradigm for 10 weeks and withdrawal symptoms were recorded after administration of naloxone (3mg/kg). One month exposure to constant light resulted in a significant decrease of melatonin concentration in the LL group. In addition, mRNA levels of Per2 and dopamine D1 receptor were up-regulated in both the striatum and prefrontal cortex of the LL group. However, expression of Per1 gene was only up-regulated in the striatum of LL rats in comparison to LD animals. Furthermore, after one month exposure to constant light, morphine consumption and preference ratio and also severity of naloxone-induced withdrawal syndrome were significantly greater in LL animals. It is concluded that exposure to constant light by up-regulation of Per2 and dopamine D1 receptor in the striatum and prefrontal cortex and up-regulation of Per1 in the striatum and the possible involvement of melatonin makes animals vulnerable to morphine preference and addiction.