The Action of Adrenergic Agonists and Antagonists in the Present of Bupropion in the Vta Nucleus on Morphine Withdrawal Syndrome on Episodic Behaviors in Rats

Bupropion is a unique and non-nicotine smoke cessation agent, and it is using smoke cessation drugs under FDA approval despite its antidepressant effect. In the current study, we considered the short-term interaction of bupropion, adrenoceptors proprietary agonists and antagonists (phenylephrine, prazosin, clonidine and yohimbine) in intra VTA injection on naloxone precipitated withdrawal symptoms. The injection guide cannulae were implanted into VTA nuclei according to stereotaxic surgery under sterile conditions. The sham group was received saline as a drug vehicle, but treated groups received 2.5 mg/μl/min of bupropion alone and with doses of phenylephrine (0.2 µg/µl/minute), prazosin (1 µg/µl/minute), clonidine and yohimbine (2 µg/µl/minute) 20 before bupropion. Dependent and non-dependent control groups had surgery, but they had no intra-VTA injection. In each treatment group, 8 rats were used. Withdrawal signs were precipitated by naloxone (1.2 mg/Kg, s.c.), observed continuously and registered online each minute. The behaviors captured by 3 digital cameras indifferent view (30 min) for offline analysis. Signs were counted and analyzed within and between groups. The results showed that intra-VTA bupropion can alter the occurrence of withdrawal symptoms and decrease more of them. Adrenoceptor agonists decrease some of the symptoms. This decrease was significant statistically in comparison with sham and control groups and between treatment groups. Occurrence extents of withdrawal symptoms have no significance statistically in naive control and sham groups toward the witness group. Results showed adrenergic system has a role in the opioid system and drug dependence; also between influences extent of adrenoceptor's species is a difference in accession of diverse withdrawal signs.