Influence of L-NAME in the Ventral Tegmental Area in the Improving Effect of Nicotine on Amnesia Induced by Morphine on Adult Male Rats

Subject Areas : Journal of Animal Biology

مرتضی پیری ¹ , مریم السادات شاهین ² , مسعود ملکی ³ , محمدرضا زرین دست ⁴

1 - دانشگاه آزاد اسلامی، واحد اردبیل، مربی گروه زیست شناسی، اردبیل، ایران
2 - دانشگاه آزاد اسلامی، واحد شهر ری، عضوباشگاه پژوهشگران جوان، شهر ری، ایران
3 - دانشگاه آزاد اسلامی، واحد اردبیل، مربی گروه زیست شناسی، اردبیل، ایران
4 - دکتری داروسازی ، استاد گروه فارماکولوژی، دانشکده پزشکی و مرکز ملی مطالعات اعتیاد، دانشگاه علوم پزشکی تهران

Received: 2014-06-23 Accepted : 2017-05-21 Published : 2010-10-23

Keywords: Rat, L-NAME, Ventral tegmental area, nicotine,

Abstract :

Nitric oxide synthase has been detected in ventral tegmental area, which is a key brain region that seems mediate behavioral effect of morphine and nicotine. In the present study, the possible involvement of L-NAME, a nitric oxide synthase inhibitor, in the ventral tegmental area in nicotineandrsquo;s effect on morphine state-dependent learning was investigated. This experimental study was performed on 300 Adult male Wistar rats. Rats were anesthetized with ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Two stainless-steel cannuale were placed in the ventral tegmental area. The animals trained in a step-through type inhibitory avoidance task, and tested 24h after training to measure step-through latency for the assessment of memory in male Wistar rats.Post-training or pre-test injection of morphine (5 and 7.5 mg/kg) caused amnesia. The amnesia induced by post-training administration of morphine restored by pretest injection of morphine (5 and 7.5 mg/kg) or nicotine (0.5 and 1 mg/kg). Interestingly, pre-test co-administration of ineffective doses of nicotine (0.05 and 0.1 mg/kg) plus ineffective dose of morphine (2.5 mg/kg) reversed the amnesia induced by morphine. Pre-test injection of L-NAME (1 and 2 andmicro;g/rat, intra-VTA) by itself impairs memory and prevents the nicotine reversal of morphine effect on memory. The ensemble of these observations suggests that morphine-induced state-dependent learning can be modulated through the nicotinic and nitric oxide systems.