Evaluation of the Effect of Intraperitoneal and Intracerebroventricular Injection of Vitamin B6 on Positive Reinforcing Effect of Morphine in Conditioned Place Preference (CPP) Model in Male Rat

GABAergic system in ventral tegmental area (VTA) and nucleus accumbens (NAc) plays critical role in opiate reinforcement. On the other hand, vitamin B6 has a role in formation of different neurotransmitters such as GABA. The aim of this study was to investigate the effect of intraperitoneal (ip) and intracerebroventricular (icv) injection of vitamin B6 on positive reinforcing effect of morphine in male rat. Ninety male rats were divided into treatment and control groups (15×6). This experimental study took place on six consecutive days, which consisted of three distinct phases: preconditioning, conditioning and postconditioning. For intracerebroventricular study, a sterile guide cannula was stereotaxically placed in left ventricle. After conditioning by morphine (5mg/kg, ip), on day 6 different doses of vitamin B6 were injected intrapertioneally (5, 15 and 40 mg/kg) and intracerebroventriculary (5 and 10µg/rat). Control groups received saline instead these drugs. Intraperitoneal injection (ip) of different doses of morphine induced CPP (P<0.001). Intraperitoneal injection of different doses of vitamin B6 alone did not induce any significant CPP or CPA. But, co-administration of vitamin B6 and morphine, significantly induced CPA (P<0.05) and this effect potentiated in icv injection in dose dependent maneuver manner (P<0.05 and P<0.01, respectively). It seems that vitamin B6 reduce morphine reinforcement through affecting GABAergic VTA neurons and subsequent decrease in NAc dopamine release. Therefore, it can be candidate for control or treatment of morphine craving and relapse in their dependent subjects.