Effects of chronic administration of nicotine on prolactin release in the rat: inactivation of prolactin response by repeated injections of nicotine.

The effects of chronic injections of nicotine on nicotine-induced prolactin release in the rat were measured and compared to the effects of this treatment on [3H]acetylcholine binding to nicotinic cholinergic sites in the hypothalamus. Treatment with nicotine for 10 days (s.c. injections twice daily) abolished prolactin release in response to an acute i.v. injection of nicotine given 2, 6 or 8 days after the last of the chronic injections of nicotine. At each of these time points, the binding of [3H]acetylcholine in the hypothalamus from rats treated chronically with nicotine was significantly higher than in the hypothalamus from control rats. By 14 days after the last chronic injection of nicotine, the prolactin response to an acute injection of nicotine was restored. Coinciding with the return of the nicotine-induced prolactin response, the binding of [3H]acetylcholine had returned to control values. These results are consistent with the hypothesis that nicotine inactivates nicotinic cholinergic receptors in brain by an allosteric mechanism, and that prolonged inactivation of nicotinic cholinergic receptors leads to their increased number.