| BackgroudAntipsychotic drug-induced sexual dysfunction is an important and problematic side effect, which may diminish a patient's quality of life and lead to treatment non-compliance. To date, most work on sexual side effects induced by antipsychotics has focused on epidemiological aspects, which may be limited by a variety of influences and confounders that are difficult to avoid, for example disease symptoms, the privacy of human sexual behaviour etc. However, few studies have investigated mechanisms and processes of drug-induced sexual dysfunction at a more basic level. Consequently, it would be of value to assess in animals the effects of current or potential antipsychotics, with the expectation that the results would allow us to further explore the mechanisms involved in this side effect. Such study will play an important role for our understanding of antispsychotic drug-induced male sexual dysfunction and contribute to clinical individual treatment.Objective1. To build an animal model of antipsychotics induced sexual dysfunction and to investigate the effect of chronic antipsychotic treatment on sexual behaviour and genital organ size in the male rat.2. To assess the effect of chronic antipsychotic treatment on sex hormones of pituitary-gonadal axis in the male rat, and the effect of treatment on gene expression and activity of nitric oxide synthase (NOS) in the penile cavernous tissue of male rats.MethodsPart oneA total of 80, 3-month-old male SD rats were divided randomly into four groups, which were orally administered with risperidone (2 mg/kg), haloperidol (2 mg/kg), quetiapine (20 mg/kg)and vehicle (distilled water) respectively for three or six weeks. Their mating behaviors were evaluated after treated by antipsychotics for three or six weeks by using receptive female rats. The following day the rats were killed. Those testis, epididymis, seminal vesicle and prostate were weighted and those indices of genital organs were measured subsequently. The serum sample and penile cavernous tissue were also collected. Part two1. The serum concentration of testosterone and lutuneizing hormone (LH) was assayed by double antibody radioimmunoassay (RIA).2. MRNA expressions of three subtype NOS in the penile cavernous tissue were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). And NOS activity of the penile cavernous tissue was also examined.ResultsPart oneThe following sexual competence was significantly impaired in both risperidone group and haloperidol group at three weeks: libido (assessed in numbers of mounting and intromission), sexual arousability/motivation (in terms of latencies for mounting, intromission), orgasm (in terms of latency for ejaculation) (U7=6.5-23; P<0.05~<0.001) . At six weeks, haloperidol also suppressed hit ratio beside above-mentioned parameters, indicating erectile dysfunction( U= 19; P=0.019). However, risperidonehad not significant effect on sexual function at six weeks. At three weeks, epididymis weight and indices were significantly decreased in both risperidone group and haloperidol group (t=—3.309-—4.081; P=0.001~ 0.004) . At six weeks, the weight and indices of epididymis, seminal vesicle and prostate were significantly reduced in haloperidol group (t= —3.615-—6.077; PO.001-P=0.002) , but not in risperidone group. In contract, quetiapine had no effect on the indices of sexual organ and sexual function as compared with control group at three weeks and six week respectively. Part two1. In haloperidol and risperidone group, the serum level of testosterone were decreased at six weeks (risperidone: t=4A42, P— 0.001; haloperidol: f=4.053, P=0.002) , but not at three weeks. The serum level of LH was not influenced by haloperidol and risperidone. Quetiapine had no effect on serum sex hormones. Spearman correlation analysis showed that serum concentration of testosterone had significant positive relationship with sex organ weight ( r=0.274~0.369; P=0.001~0.004) .2. Compared with the control group, the expression of eNOS mRNA was significantly red... |
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