COMPARISON OF SEROTONIN RECEPTOR NUMBERS AND ACTIVITY IN SPECIFIC HYPOTHALAMIC AREAS OF SEXUALLY ACTIVE AND INACTIVE FEMALE RATS

In a previous study we have shown that a positive correlation exists b etween 5-hydroxytryptamine (5-HT) activity and female sexual receptivi ty in the pre-optic area (POA) and median eminence (ME) and that there is a negative correlation in the ventromedial nucleus (VMN), zona inc erta (ZI) and arcuate nucleus (ARC). In this report, the possibility t hat 5-HT receptor density and affinity alter with sexual receptivity h as been investigated. Micropunches of the POA, VMN, ARC, ME and the an terior hypothalamus were dissected from ovariectomised rats primed wit h a submaximal steroid regime (2 mu g oestradiol benzoate, OB, followe d at 48 h by 0.05 mg progesterone) which induced receptivity (lordosis quotient, LQ, 80-100%) in approximately half the animals, the remaini ng half usually exhibiting an LQ <20%. Binding studies were carried ou t using H-3-ketanserin (5-HT2A ligand) and H-3-8-hydroxy-2-(di-n-propy lamine)tetraline (8-OHDPAT; 5-HT1A ligand) and pooled (n = 5) micropun ch samples. The B-max of 5-HT2A receptors in the sexually receptive gr oups was significantly (p < 0.05) greater in the POA and ME and signif icantly lower in the VMN, ARC and ZI when compared with values in the non-receptive animals. The K-D values of the 5-HT2A receptors did not differ in the two groups (except the ZI, where the K-D was lower in re ceptive rats). Neither the B-max nor K-D of the 5-HT1A receptors diffe red in the two groups in any area investigated. Administration of the 5-HT2 agonists dimethoxyiodophenylaminopropane and m-chlorophenyl pipe razine into the POA resulted in enhanced sexual activity in animals ex hibiting a low level of receptivity, after 5 mu g OB given alone while ketanserin (5-HT2A antagonist) in the POA inhibited sexual activity i n receptive animals primed with the submaximal steroid regime given ab ove. In the same models, neither the 5-HT2 agonists nor the 5-HT2A ant agonist affected behaviour when applied to the VMN. The 5-HT1A agonist 8-OHDPAT exerted an inhibitory effect in the VMN. These findings, tog ether with earlier results, show that in receptive animals there is an increase in both 5-HT turnover and 5-HT2A receptors in the POA and ME . Additionally 5-HT2 agonists and an antagonist applied to the POA enh ance and reduce sexual activity, respectively. This suggests that the 5-HT2 system in the POA has a stimulatory role in the control of femal e sexual behaviour. Both 5-HT activity and 5-HT2 receptors are decreas ed in the VMN, ARC and ZI of receptive animals. 5-HT2 agonists and a 5 -HT2A antagonist have no effect in the VMN indicating that there is no 5-HT2-stimulatory or -inhibitory effect in this area, at least in the animal models used in these experiments. However, the VMN is a site o f an inhibitory action mediated by the 5-HT1A receptors.