Borkar Chandrashekhar D, Upadhya Manoj A, Shelkar Gajanan P, Subhedar Nishikant K, Kokare Dadasaheb M
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, India.
Pharmacology Department, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, India.
Addict Biol. 2016 Jul;21(4):766-75. doi: 10.1111/adb.12254. Epub 2015 Apr 30.
Although modulatory effects of neuropeptide Y (NPY) on ethanol consumption are well established, its role in ethanol reward, in the framework of mesolimbic dopaminergic system, has not been studied. We investigated the influence of nucleus accumbens shell (AcbSh) NPYergic system on ethanol self-administration in posterior ventral tegmental area (p-VTA) using intracranial self-administration paradigm. Rats were stereotaxically implanted with cannulae targeted unilaterally at the right p-VTA and trained to self-administer ethanol (200 mg%) in standard two-lever (active/inactive) operant chamber, an animal model with high predictive validity to test the rewarding mechanisms. Over a period of 7 days, these rats showed a significant increase in the number of lever presses for ethanol self-administration suggesting reinforcement. While intra-AcbSh NPY (1 or 2 ng/rat) or [Leu(31) , Pro(34) ]-NPY (0.5 or 1 ng/rat) dose-dependently increased ethanol self-administration, BIBP3226 (0.4 or 0.8 ng/rat) produced opposite effect. The rats conditioned to self-administer ethanol showed significant increase in the population of NPY-immunoreactive cells and fibres in the AcbSh, central nucleus of amygdala (CeA), hypothalamic arcuate nucleus (ARC) and lateral part of bed nucleus of stria terminalis as compared with that in the naïve rats. Neuronal tracing studies showed that NPY innervations in the AcbSh may derive from the neurons of ARC and CeA. As NPY and dopamine systems in reward areas are known to interact, we suggest that NPY inputs from ARC and CeA may play an important role in modulation of the dopaminergic system in the AcbSh and consequently influence the ethanol induced reward and addiction.
虽然神经肽Y（NPY）对乙醇消耗的调节作用已得到充分证实，但其在中脑边缘多巴胺能系统框架下对乙醇奖赏的作用尚未得到研究。我们使用颅内自我给药范式，研究了伏隔核壳（AcbSh）NPY能系统对后腹侧被盖区（p-VTA）乙醇自我给药的影响。将大鼠立体定位植入单侧靶向右侧p-VTA的套管，并在标准的双杠杆（主动/非主动）操作箱中训练其自我给药乙醇（200mg%），这是一种具有高预测效度的动物模型，用于测试奖赏机制。在7天的时间里，这些大鼠自我给药乙醇时的杠杆按压次数显著增加，表明有强化作用。虽然向AcbSh内注射NPY（1或2 ng/只大鼠）或[Leu(31), Pro(34)]-NPY（0.5或1 ng/只大鼠）能剂量依赖性地增加乙醇自我给药，但注射BIBP3226（0.4或0.8 ng/只大鼠）则产生相反的效果。与未接触乙醇的大鼠相比，经条件训练自我给药乙醇的大鼠在AcbSh、杏仁核中央核（CeA）、下丘脑弓状核（ARC）和终纹床核外侧部的NPY免疫反应性细胞和纤维数量显著增加。神经元追踪研究表明，AcbSh中的NPY神经支配可能来自ARC和CeA的神经元。由于已知奖赏区域中的NPY和多巴胺系统相互作用，我们认为来自ARC和CeA的NPY输入可能在调节AcbSh中的多巴胺能系统中起重要作用，从而影响乙醇诱导的奖赏和成瘾。
