the effect of chronic antipsychotic drug on hypothalamic expression of neural nitric oxide synthase and dopamine d2 receptor in the male rat慢性抗精神病药物的影响下丘脑神经元一氧化氮合酶的表达和多巴胺d2受体的雄性老鼠.pdfVIP

The Effect of Chronic Antipsychotic Drug on Hypothalamic Expression of Neural Nitric Oxide Synthase and Dopamine D2 Receptor in the Male Rat Xiang Rong Zhang1,2,3., Ying Xin Wang1,2., Zhi Jun Zhang1,2*, Lei Li1,2, Gavin P. Reynolds3,4 1 Department of Neuropsychiatry, Affiliated Zhongda Hospital of Southeast University, Nanjing, China, 2 Neuropsychiatric Research Institute, School of Medicine, Southeast University, Nanjing, China, 3 Department of Psychiatry, School of Medicine and Dentistry, Queen’s University Belfast, United Kingdom, 4 Biomedical Research Centre, Sheffield Hallam University, Sheffield, United Kingdom Abstract Antipsychotic-induced sexual dysfunction is a common and serious clinical side effect. It has been demonstrated that both neuronal nitric oxide (nNOS) and dopamine D2 receptor (DRD2) in the medial preoptic area (MPOA) and the paraventricular nucleus (PVN) of the hypothalamus have important roles in the regulation of sexual behaviour. We investigated the influences of 21 days’ antipsychotic drug administration on expression of nNOS and DRD2 in the rat hypothalamus. Haloperidol (0.5 mg/kg/day i.p.) significantly decreased nNOS integrated optical density in a sub-nucleus of the MPOA, medial preoptic nucleus (MPN), and decreased the nNOS integrated optical density and cell density in another sub-nucleus of the MPOA, anterodorsal preoptic nucleus (ADP). Risperidone (0.25 mg/kg) inhibited the nNOS integrated optical density in the ADP. nNOS mRNA and protein in the MPOA but not the PVN was also significantly decreased by haloperidol. Haloperidol and risperidone increased DRD2 mRNA and protein expression in both the MPOA and the PVN. Quetiapine (20 mg/kg/day i.p.) did not influence the expression of nNOS and DRD2 in either the MPOA or the PVN. These findings indicate that hypoth