Differential effects of gonadal steroids on dopamine metabolism in mesolimbic and nigro-striatal pathways of male rat brain

Abstract

Thirty days after castration the concentration of dopamine (DA) was significantly reduced in the septum and n. accumbens septi, but not in the caudate-putamen, of male rat brain. The concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the principle metabolites of DA, also tended to be lower in septum and n. accumbens septi after castration. Chronic s.c. administration of testosterone (T), estradiol (E2), 5 alpha-dihydrotestosterone (DHT), or E2 plus DHT in silastic capsules effectively reversed these effects of castration in septum and n. accumbens septi without affecting concentrations of DA, DOPAC, or HVA in caudate-putamen. The accumulation of DOPA after inhibition of aromatic amino acid decarboxylase activity, which was taken as an in vivo index of tyrosine hydroxylase activity, was not affected in these brain regions by long-term castration or by chronic administration of DHT to castrated males. Acute administration of haloperidol caused equivalent, significant increments in concentrations of DOPAC and HVA in all brain regions studied, regardless of whether castrated rats had been implanted with DHT capsules or no hormone. However, in the absence of haloperidol treatment the concentration of DOPAC in septum and n. accumbens septi, but not in caudate-putamen, was significantly higher in castrated rats implanted with DHT as opposed to no hormone. These results suggest that chronic exposure to T, or to its neural metabolites, E2 and DHT, selectively enhances metabolic activity in mesolimbic DA neurons.