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.
Highlights
Antipsychotic-induced sexual dysfunction is a common and serious clinical side effect, which is gaining increasing attention within the past decade
The current study investigated the expression of neural nitric oxide synthase (NOS) and the dopamine D2 receptor in the medial preoptic area (MPOA) and paraventricular nucleus (PVN) after chronic systemic administration of the typical antipsychotic haloperidol, and the atypical antipsychotics risperidone and quetiapine, in which haloperidol and risperidone, but not quetiapine are associated with a high incidence of sexual dysfunction in both humans [22,23] and rats [9]
Individual comparisons with vehicle group revealed that integrated optical density (IOD) of neural NOS (nNOS) staining in the anterodorsal preoptic nucleus (ADP) was significantly reduced by three weeks administration of haloperidol (p = 0.038) and risperidone (p = 0.049), but not by quetiapine (p = 0.989)
Summary
Antipsychotic-induced sexual dysfunction is a common and serious clinical side effect, which is gaining increasing attention within the past decade. The sensory information related to sexual behaviour is processed at various brain nuclei, which balance the inhibitory and excitatory influence on spinal sympathetic and parasympathetic centres, and determine the functional state of the sexual effector organ [6]. Antipsychotics might act both centrally and peripherally to induce sexual dysfunction. Research directly investigating the central mechanisms of antipsychotic-induced sexual dysfunction is rare. Understanding of these mechanisms is mostly theoretical, deriving from general knowledge of sex physiology and psychopharmacology, and is generally unverified by basic or clinical investigation
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