UBC Theses and Dissertations
Serotonin receptor subtypes and sexual behaviour in the female rat Mendelson, Scott Douglas
Recently, it has been discovered that serotonin (5-HT) receptors exist as subtypes in the mammalian brain. At least two major subtypes that differ in their distribution, and affinity for serotonergic drugs, have now been described. These receptors have been labeled 5-HT₁, and 5-HT₂ receptors. The purpose of this thesis is to determine what roles the 5-HT₁, and 5-HT₂ receptors might play in the modulation of sexual behaviour in the female rat. The administration of the 5-HT₂ receptor antagonist pirenperone inhibited sexual receptivity in adult, ovariectomized Sprague Dawley rats that had been primed either chronically with estradiol benzoate (EB), or acutely with EB plus varying doses of progesterone (P). An inhibition occurred at peripherally administered doses of 50, 100 and 150, but not 25 µg/kg of pirenperone. Pirenperone also inhibited receptivity when administered intraventricularly at a dose of 15 µg/kg, however this dose of pirenperone was ineffective when administered peripherally. Increasing the dose of P did not attenuate the inhibitory effect of pirenperone. The 5-HT₂ antagonists ketanserin (2.5 mg/kg) and spiperone (250 µg/kg) also inhibited receptivity in females that had been primed with EB plus P. The inhibitory effect of pirenperone was attenuated by the 5-HT₂ agonist quipazine , however the 5-HT precursor 5-hydroxytryptophan (5-HTP) (20 mg/kg), and the 5-HT₁, agonists 5-methoxy-N,N-dimethytryptamine (5MeODMT) (200 µg/kg) and tryptamine (2 mg/kg) did not attenuate the effect of pirenperone. Quipazine, 5-HTP, and 5MeODMT did not effect receptivity in females that had been primed with EB plus P, however tryptamine inhibited receptivity. Whereas the nonselective 5-HT antagonist methysergide (3 mg/kg) failed to have an effect on receptivity in females that had been primed with EB, methysergide coadministered with quipazine facilitated receptivity. Pirenperone also inhibited proceptivity in females that had been primed with EB plus P. Although quipazine did not attenuate the inhibitory effect of pirenperone upon proceptivity, quipazine alone facilitated proceptivity in females that had been primed either with EB, or with EB and P. Methysergide did not effect proceptivity, and 5-HTP, 5MeODMT, and tryptamine were also ineffective with regards to proceptivity. The results of the present series of experiments are not entirely consistent with Meyerson's widely held theory of serotonergic inhibition , rather they suggest a dual role for 5-HT in female sexual behaviour. Therefore, a new theory regarding the role of 5-HT in sexual behaviour is proposed. Specifically, it is proposed that inhibitory effects of 5-HT are mediated by activity at 5-HT₁, receptors, whereas facilitatory effects are mediated by activity at 5-HT₂ receptors.
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