Effect of prolonged exposure to nicotine and stress on the pituitary-adrenocortical response; the possibility of cross-adaptation.

Daily IP injections of nicotine (200 micrograms/kg body weight) resulted in an adaptation of the nicotine induced rise in plasma corticosterone. By 30 days the plasma corticosterone rise was not significantly different from that seen in control animals receiving an injection of saline. A similar adaptation to the plasma corticosterone response to the stress of signalled, irregular footshock was also observed. However, in the case of the exposure to stress, while the corticosterone response at day 40 was significantly less than the response seen on day 1, it was still significantly greater than the plasma corticosterone level from unstressed control animals. Cross-adaptation experiments were conducted in which animals were adapted to the steroidogenic action of nicotine and then subjected to a novel exposure to footshock stress, and vice versa. In both situations the animals responded to the novel stimulus, either stress or nicotine, with a significant rise in plasma corticosterone. It was postulated that nicotine and psychological stress act upon the hypothalamo-pituitary-adrenal axis via functionally separate pathways at the level of the corticotrophin releasing factor neuron. The separate pathways appear to differ in their ability to be inhibited by corticosterone feedback.