Nicotine and its major metabolite cotinine have different effects on aldosterone and prolactin serum levels in the normal male rat.

Nicotine (0.01-1.0 mg/kg, i.p.) or cotinine (0.003-1.0 mg/kg, i.p.) treatment was administered to Sprague-Dawley male rats. The time-effect curves (5, 10, 30, 60 and 180 min) were analyzed. Nicotine dose-dependently increased blood aldosterone and corticosterone levels with a peak effect 10 min after the intraperitoneal injection. Nicotine treatment weakly decreased serum levels of aldosterone at 2 h, possibly as a consequence of nicotine metabolising to cotinine, resulting in higher serum levels of cotinine than nicotine. Cotinine dose-dependently reduced serum aldosterone levels, an effect which became more marked with time, leaving plasma corticosterone unchanged. Nicotine dose-dependently increased serum prolactin levels at 5 and 10 min following treatment, an effect which had diminished at 30 min. Cotinine dose-dependently reduced serum prolactin levels at 5 min followed by a dose-dependent increase at 10 min after which a dose-dependent reduction was again found after 30 min post treatment. In conclusion, acute nicotine and cotinine treatment produced opposite effects on aldosterone and prolactin serum levels. The prolonged effect of cotinine on aldosterone levels may be involved in changes in brain function, and may be connected to the development of withdrawal effects after stopping cigarette smoking. As reported by other investigators, nicotine produced enhanced plasma corticosterone levels while cotinine treatment was ineffective. Since cotinine induced marked changes in serum prolactin levels while leaving LH levels unchanged, it seems plausible that cotinine affects neuroendocrine regulation via mechanisms not primarily related to circulatory effects. Thus, an action at the median eminence--pituitary level seems likely.