The effect of nicotine on central catecholamine neurons and gonadotropin secretion. III. Studies on prepubertal female rats treated with pregnant mare serum gonadotropin

The effects of nicotine and its main metabolite cotinine have been evaluated on central catecholamine (CA) levels and turnover and gonadotropin secretion in prepubertal female rats treated with pregnant mare serum (PMS) gonadotropin. The effects on ovulation were also evaluated. PMS was administered on day 30 s.c. resulting in a critical period in the afternoon of day 32. All the pharmacological experiments were performed in relation to the critical period. The serum FSH, LH and prolactin levels were determined by radioimmunoassay procedures. The CA levels and turnovers in various hypothalamic and telencephalic CA systems were studied by quantitative microfluorimetry. Nicotine was found to delay the hypersecretion of prolactin and LH in relation to the critical period in the afternoon of day 32, whereas no corresponding delay was apparent in the secretion of FSH. Nicotine in repeated doses of 1 mg/kg, did not influence ovulation as measured by number of eggs and proportion of non-ovulating rats. Cotinine (25-50 mg/kg) given at 4.00 p.m. on day 32 significantly reduced the number of eggs. The percentage of non-ovulating rats was also increased by cotinine. Nicotine significantly reduced the increase in prolactin secretion caused by H 44/68. Cotinine + H 44/68 treatment during the critical period also reduced the serum LH levels. Nicotine significantly reduced the CA stores in the medial palisade zone (MPZ) of the median eminence and also significantly increased the dopamine (DA) turnover in the lateral palisade zone (LPZ). Cotinine, on the other hand, markedly reduced the noradrenaline (NA) turnover in the subependymal layer leaving the CA turnover in the external layer unaffected. In the forebrain the only significant change after nicotine treatment was a depletion of DA stores in the tuberculum olfactorium. Studies on intraindividual correlations between serum prolactin levels and CA levels in various regions of the brain revealed significant correlation in the subependymal layer in the group treated with nicotine and H44/68 and in the group treated with cotinine and H44/68. The present results support the idea that nicotine can reduce and delay LH and prolactin secretion via an activation of the lateral and medial tubero-infundibular DA systems, respectively. It is postulated that the actions described above may be partly mediated over nicotinic acetylcholine receptors, controlling activity in the median eminence DA and NA nerve terminals.