Effects of hormone replacement therapy on mesolimbic extracellular dopamine stress: an in vivo microdialysis study

ABSTRACT

OBJECTIVE: To determine the effects of hormone replacement therapy on dopamine (DA) release in the nucleus accumbens septi (NAS) of rats following footshock stress and to correlate these effects with locomotory behaviour. DESIGN AND METHODS: Thirty-two Long Evans rats were ovariectomized and treated with oestradiol benzoate, progesterone or oil (control group). Rats were stereotaxically implanted with guide cannulae in the NAS and dialysis probes used to sample the extra-cellular fluid (ECF). Following baseline measurements, intermittent footshocks were delivered for 10 minutes, and dialysate DA levels and locomotor activity assessed over 20 minute intervals for 2 hours by high performance liquid chromatography and a photocell activity monitor, respectively. RESULTS: At baseline, hormone replacement significantly decreased DA levels in the NAS. Oestrogen treated rats had the lowest DA release at baseline (p<0.001). Following footshock, all groups exhibited significant increases in DA levels; oestrogen treated rats showed the most significant relative increase, but absolute levels remained lowest. Locomotor activity at baseline was highest in oestrogen treated rats and showed no change after footshock, remaining higher than in other groups. All other groups showed relative increase in activity after footshock (p=0.02). CONCLUSIONS: Oestrogen pre-treatment depresses baseline DA level in the NAS, but enhances relative levels after footshock, while suppressing changes in locomotor activity. There is a general reciprocal relationship between DA levels within ECF and locomotor activity in all groups. This finding may have implications for understanding of the processes regulated by NAS dopamine, e.g. addiction or associative learning.(Au)