Summary: | The present series of experiments was designed to investigate the potential inhibitory influence
of stress and stress-related hormones on the 5-HT2A receptor-mediated behavioural effects of
risperidone, an atypical antipsychotic. Experiment 1 examined the effects of chronic risperidone
treatment; Long-Evans male rats were assigned to a daily regimen of either corticosterone (20
mg/kg) or vehicle for 14 days. Risperidone was administered at a dose of 0.1 mg/kg for 14 days
prior to testing. Rats were tested on measures of sexual behaviour and wet dog shakes (WDS),
both 5-HT2A receptor-mediated behaviours. Consistent with previous findings, chronic
corticosterone treatment induced behavioural changes indicative of an increase in 5-HT2A
receptor activity. Results from Experiment 1 demonstrated the efficacy of risperidone in
facilitating rat sexual behaviour and inhibiting WDS frequency. Of interest, the behavioural
effects of risperidone were significantly attenuated by a chronic corticosterone regimen. In
Experiment 2, the behavioural influence of chronic mild stress (CMS) on a chronic risperidone
regimen was examined. Rats received daily injections of either risperidone (0.1 mg/kg) or saline
and were exposed daily to either CMS or no stress for 21 days. Similar to findings using a
chronic corticosterone regimen, CMS significantly attenuated the effects of risperidone on both
male rat sexual behaviour and WDS expression. Experiment 3 investigated the possibility that
chronic CMS treatment act via elevated corticosterone levels when influencing the behavioural
efficacy of risperidone. Rats received risperidone and metyrapone (50 mg/kg), a corticosterone
synthesis inhibitor, on a daily basis for a period of 14 days. Results from Experiment 3 indicated
the effects of stress on WDS frequency, but not on sexual behaviour, in risperidone-treated rats
are likely mediated by corticosterone. Taken together, the data implicate both corticosterone and
stress as playing an inhibitory role on the behavioural efficacy of risperidone. The current
findings may help to explain the high incidence of psychotic patients who are non-responsive to
their medications and demonstrate elevated levels of stress-related hormones. === Arts, Faculty of === Psychology, Department of === Graduate
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