Oestrogen modulation of the effect of 8-OH-DPAT on prepulse inhibition: effects of aromatase deficiency and castration in mice.

OBJECTIVE

The aim of this study was to investigate the interaction of sex steroid hormones, particularly oestrogen, in the regulation of prepulse inhibition (PPI) by serotonin-1A (5-HT1A) receptors.

MATERIALS AND METHODS

We studied aromatase knockout (ArKO) mice, which are unable to produce oestrogen but have high levels of testosterone, and the effects of castration.

RESULTS AND DISCUSSION

Treatment of male ArKO mice with the 5-HT1A receptor agonist, 8-hydroxy-dipropyl-aminotetralin (8-OH-DPAT), caused an increase in PPI that was significantly greater than in male wild-type controls. Castration of male mice caused a significant enhancement of the effect of 8-OH-DPAT in control mice; however, there was no change in the effect of this drug in ArKO mice. There was no significant effect of 8-OH-DPAT on PPI in either female ArKO or wild-type controls. In all experiments, the effects of 8-OH-DPAT on startle were not different between the groups. [3H]8-OH-DPAT autoradiography showed no differences in 5-HT1A receptor binding densities in areas of the forebrain, hippocampus or raphe region that could explain the PPI results. These data show that the absence of oestrogen in male ArKO mice leads to a greater effect of 5-HT1A receptor stimulation on PPI. This effect can be mimicked in male control mice by castration. The differential involvement of oestrogen and testosterone in these animal models is discussed.