Nicotine modulates effects of stress on acoustic startle reflexes in rats: dependence on dose, stressor and initial reactivity.

Cigarette smokers report that one reason for smoking is that smoking helps them cope with stress, but there is conflicting evidence as to whether nicotine reduces physiological and behavioral responses to stress. The acoustic startle reflex amplitude, pre-pulse inhibition, and habituation of the reflex provide quantifiable measures of behavioral reactivity that may be sensitive to stress-induced changes that are altered by nicotine. In the present experiment, rats classified as high and low reactors according to baseline startle amplitudes were administered nicotine (6 or 12 mg/kg/day) or saline by osmotic minipump for 11 days. On day 11, animals were acutely stressed by restraint or observation of restraint of conspecifics prior to startle measurement. Nicotine and stress each independently increased acoustic startle amplitude and amount of pre-pulse inhibition, but in combination, the effect of restraint stress and 12 mg/kg nicotine were indistinguishable from saline-treated, non-stressed controls. In contrast, the 6 mg/kg nicotine dose enhanced effects of both restraint and observation stressors on startle amplitude and pre-pulse inhibition. Animals classified as highly reactive prior to treatment were more responsive to nicotine, stress, and the combination, suggesting that initial reactivity is an important determinant of drug and stress effects. Results indicate that nicotine can both reduce and enhance stress effects on reflex amplitude and pre-pulse inhibition depending upon nicotine dose, stressor, and individual differences in reactivity.