The effects of female sex steroids on central serotonergic neurotransmission

• Main Author: Shanks, Elaine Anne
• Format: Dissertation
• Language: English
• Published: University of Edinburgh 1999

Acutely ovariectomised adult female Wistar rats were used to study the ability of oestrogen and progesterone to alter central 5-HT neurotransmission, with particular interest in changes in 5-HT2A receptor and serotonin transporter (SERT) binding site density and the firing characteristics of 5-HT neurones in the dorsal raphe nucleus (DRN). Changes in 5-HT2A binding site density were evaluated using quantitative autoradiography on serial coronal sections using [3H]MDL 100,907 and [3H]ketanserin with non-specific binding being assessed using RP 62203. Binding site density was measured in the dorsal and median raphe nuclei, which contain serotonergic cell bodies, and regions of the forebrain which receive projections from these raphe nuclei e.g. the cortex and hypothalamus. The experiments examined the effects of oestrogen and progesterone on binding site density while also comparing the binding patterns of the two 5-HT2A receptor ligands. Preliminary experiments were carried out using coronal sections containing cingulate cortex to obtain the optimal conditions for [3H]MDL 100,907 binding experiments. Similar binding patterns were observed throughout the brain using [3H]MDL 100,907 or [3H]ketanserin although higher non-specific binding was observed with ketanserin. Specific binding levels differed between the two ligands with higher levels being observed in the cingulate cortex, nucleus accumbens and olfactory tubercle and lower levels in the amygdala and dorsal raphe using [3H]MDL 100,907 compared to [3H]ketanserin. Acute oestrogen treatment produced no significant differences in binding site density in any of the regions examined when [3H[MDL 100,907 was used; however, an increase in binding was observed with [3H]ketanserin in the cingulate and frontal cortex. Progesterone treatment alone or in combination with oestrogen produced no significant differences in binding site density in any of the regions examined with either [3H]MDL 100,907 or [3H]ketanserin. These results suggest that progesterone has no effect alone but can attenuate the effect of oestrogen on ketanserin binding in specific brain regions.