title: The effect of chronic antipsychotic drug on hypothalamic expression of neural nitric oxide synthase and dopamine D2 receptor in the male rat.
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 hypothalamic nNOS and DRD2 are affected to different extents by chronic administration of risperidone and haloperidol, but are unaffected by quetiapine. These central effects might play a role in sexual dysfunction induced by certain antipsychotic drugs.
authors.affiliation: Department of Neuropsychiatry, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.
authors.forename: Xiang Rong
authors.initials: XR
authors.lastname: Zhang
authors.forename: Ying Xin
authors.initials: YX
authors.lastname: Wang
authors.forename: Zhi Jun
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D018967:Risperidone / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D052248:Nitric Oxide Synthase Type I; D006220:Haloperidol; D018967:Risperidone