Postnatal administration of allopregnanolone modifies glutamate release but not BDNF content in striatum samples of rats prenatally exposed to ethanol

Abstract

Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABAA receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c.) administered to juvenile male rats (day 21 of age) on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8). Prenatal ethanol administration decreased the K(+)-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABAA receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.

Figure 1

Panel (a): ³H-Glu uptake from rat striatal slices; Panel (b): ³H-Glu fractional release induced from rat striatal slices by 28 mM K⁺. Control (white bars) or prenatal ethanol-exposed (gray bars) male rats were injected with allopregnanolone (65 μg/kg) or vehicle on P21, 2.5 h before the experiment. Results are expressed as mean ± SEM (n = 6–9) (different letters indicate statistically significant differences).

Figure 2

Effect of allopregnanolone (65 ug/kg) on BDNF content in P21 rat striatum. Control (white bars) or prenatal ethanol-exposed (gray bars) male rats were injected with allopregnanolone or vehicle on P21, 2.5 h before the experiment. Results are expressed as mean ± SEM (n = 4-5) (different letters indicate statistically significant differences).