Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5‐HT Relationship in the Rat Suprachiasmatic Area

Abstract

The purpose of this study was to test the capacity of oestradiol to modulate the stimulating effect of a-aminobutyric acid (GABA) on serotonin (5-HT) metabolism, previously described in the suprachiasmatic area of the male rat. After an in vivo stimulation of GABA transmission by systemic administration of a GABA-transaminase inhibitor (amino-oxyacetic acid) or a GABA, agonist (RS-baclofen), the 5-HT metabolism was studied in the suprachiasmatic area of ovariectomized, and ovariectomized oestradiol-treated rats.Amino-oxyacetic acid or RS-baclofen treatment increased the endogenous content of 5-HT in the suprachiasmatic area of males and ovariectomized rats. These two treatments were without effect in ovariectomized oestradiol-treated rats. GABA transmission stimulation induced by amino-oxyacetic acid treatment failed to affect the release and synthesis of 5-HT in ovariectomized oestradiol-treated rats while it increased these two parameters of 5-HT metabolism in the suprachiasmatic area of male and ovariectomized rats. To investigate the main target of oestradiol effect, comparative studies of the serotoninergic and GABAergic metabolism in the suprachiasmatic area were performed in the three experimental groups. Under our experimental conditions the endogenous 5-HT metabolism was similar between ovariectornized and ovariectomized oestradiol-treated rats. Nevertheless, 5-HT metabolism was higher in the two female groups than in the male group. Neither GABA metabolism nor GABAergic response to GABA-related drug treatment differed between ovariectomized, and ovariectomized oestradiol-treated rats. However, the turnover of GABA was higher when compared to the two female groups. It is concluded that the lack of 5-HT responsiveness to GABA transmission stimulation in ovariectomized oestradiol-treated rats was not related to an effect of oestradiol on 5-HT metabolism or to an effect of the steroid on GABA turnover. Furthermore, our results suggest a sex difference in the activity of serotoninergic and GABAergic systems in the suprachiasmatic area.Recently, an anatomical relationship between GABAergic and szrotoninergic terminals in the suprachiasmatic nucleus (SCN) has been reported (1). Parallel to previous reports we have shown the existence of a metabolic interaction between these two neurotransmitters. The stimulation of y-aminobutyric acid (GABA) transmission leads to an increase in serotonin (5-HT) metabolism la GABA, receptor activation in the rat's suprachiasmatic area (SCA) (2, 3). The ability of oestradiol (E,) to influence neurotransmission has long been recognized. There are numerous (4-6) examples of mechanisms by which E, may act on neurotransmitter systems. These include the modulation of neurotransmitter metabolism and effects on neurotransmitter receptor concentrations. Data concerning the effects of the steroid on 5-HT and GABA metabolism in the hypothalamus are conflicting. While some authors report that E, administration to ovariectomized animals (OVX) results in no change in 5-HT content of...

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