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The neurosteroid allopregnanolone is a potent and efficacious modulator of γ-aminobutyric acid (GABA) type A receptors. The effects of intracerebroventricular injection of allopregnanolone (5 to 15 μg in 5 μl) on basal and stress-induced changes in the extracellular concentrations of dopamine were investigated by microdialysis in various brain areas of freely moving rats and compared with those of the benzodiazepine midazolam (1 to 10 μg in 5 μl). Allopregnanolone reduced (by a maximum of 65 to 75%) basal dopamine content in the prefrontal cortex and nucleus accumbens in a dose-dependent manner, but had no effect on dopamine output in the striatum. Allopregnanolone (10 to 15 μg) also completely prevented the increase in extracellular dopamine concentrations in the nucleus accumbens and cerebral cortex induced by foot-shock stress. Midazolam reduced basal dopamine content in all three brain regions studied as well as the stress- induced increase in dopamine content in the nucleus accumbens and cerebral cortex with a greater potency than allopregnanolone. These results suggest that endogenous neurosteroids may participate in the GABAergic modulation of dopaminergic transmission in the rat cerebral cortex and nucleus accumbens, two brain areas which are important in the regulation of emotional processes. These agents do not appear to affect striatal dopaminergic transmission which modulates motor function.

The oral administration of an aminoacid mixture lacking tyrosine and phenylalanine induces, in rats, a profound depletion of tyrosine in serum and in brain. Brain tyrosine is maximally depleted by 73%, 2 h after treatment, when there is a concomitant decrease in the levels of HVA (by 50%), DOPAC (by 30%) and c‐AMP (by 28%) in the basal ganglia. However, 4 to 8 h after treatment, when brain tyrosine is still depleted by 47 and 28%, respectively, DA metabolites and c‐AMP levels have returned to normal. Our findings indicate that striatal tyrosine hydroxylase is fully saturated in v i m by the concentrations of tyrosine normally present in the basal ganglia. The results also suggest indirectly that decreased DA turnover results in decreased nerve activity, as judged by the decreased cyclic AMP levels.

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