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      Comparison of Serotonin Receptor Numbers and Activity in Specific Hypothalamic Areas of Sexually Active and Inactive Female Rats

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          In a previous study we have shown that a positive correlation exists between 5-hydroxytryptamine (5-HT) activity and female sexual receptivity in the pre-optic area (POA) and median eminence (ME) and that there is a negative correlation in the ventromedial nucleus (VMN), zona incerta (ZI) and arcuate nucleus (ARC). In this report, the possibility that 5-HT receptor density and affinity alter with sexual receptivity has been investigated. Micropunches of the POA, VMN, ARC, ME and the anterior hypothalamus were dissected from ovariectomised rats primed with a submaximal steroid regime (2 µg oestradiol benzoate, OB, followed at 48 h by 0.05 mg progesterone) which induced receptivity (lordosis quotient, LQ, 80–100%) in approximately half the animals, the remaining half usually exhibiting an LQ < 20%. Binding studies were carried out using <sup>3</sup>H-ketanserin (5-HT<sub>2A</sub> ligand) and <sup>3</sup>H-8-hydroxy-2-(di-n-propylamine)tetraline (8-OHDPAT; 5-HT<sub>1A</sub> ligand) and pooled (n = 5) micropunch samples. The B<sub>max</sub> of 5-HT<sub>2A</sub> receptors in the sexually receptive groups was significantly (p < 0.05) greater in the POA and ME and significantly lower in the VMN, ARC and ZI when compared with values in the non-receptive animals. The K<sub>D</sub> values of the 5-HT<sub>2</sub>A receptors did not differ in the two groups (except the ZI, where the K<sub>D</sub> was lower in receptive rats). Neither the B<sub>max</sub> nor K<sub>D</sub> of the 5-HT<sub>1A</sub> receptors differed in the two groups in any area investigated. Administration of the 5-HT<sub>2</sub> agonists dimethoxyiodophenylaminopropane and m-chlorophenyl piperazine into the POA resulted in enhanced sexual activity in animals exhibiting a low level of receptivity, after 5 µg OB given alone while ketanserin (5-HT<sub>2A</sub> antagonist) in the POA inhibited sexual activity in receptive animals primed with the submaximal steroid regime given above. In the same models, neither the 5-HT<sub>2</sub> agonists nor the 5-HT<sub>2</sub>A antagonist affected behaviour when applied to the VMN. The 5-HT<sub>1A</sub> agonist 8-OHDPAT exerted an inhibitory effect in the VMN. These findings, together with earlier results, show that in receptive animals there is an increase in both 5-HT turnover and 5-HT<sub>2A</sub> receptors in the POA and ME. Additionally 5-HT<sub>2</sub> agonists and an antagonist applied to the POA enhance and reduce sexual activity, respectively. This suggests that the 5-HT<sub>2</sub> system in the POA has a stimulatory role in the control of female sexual behaviour. Both 5-HT activity and 5-HT<sub>2</sub> receptors are decreased in the VMN, ARC and ZI of receptive animals. 5-HT<sub>2</sub> agonists and a 5-HT<sub>2A</sub> 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 of an inhibitory action mediated by the 5-HT<sub>1A</sub> receptors.

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          Author and article information

          S. Karger AG
          09 April 2008
          : 66
          : 6
          : 384-392
          aDepartment of Obstetrics and Gynaecology, St. George’s Hospital Medical School, London, and bPfizer Central Research Ltd., Sandwich, UK
          127277 Neuroendocrinology 1997;66:384–392
          © 1997 S. Karger AG, Basel

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          Page count
          Pages: 9
          Neuroanatomy and Regulation of Hypothalamic Neurons


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