Anxiolytic effects of nicotine in a rodent test of approach-avoidance conflict.

ABSTRACT

RATIONALE Nicotine has been reported to produce both anxiolytic and/or anxiogenic effects in humans and animals. OBJECTIVES: This study examined whether pretreatment with nicotine would alter anxiety in a unique runway model of approach-avoidance conflict. MATERIALS AND METHODS: Food-restricted rats were trained to run a straight alley once a day to obtain food upon goal-box entry. Beginning on trial 11, food reward was followed by a series of five foot shocks (0.3-0.4 mA, 0.5 s) in the goal box. Non-shocked control rats continued to run for food only. The resulting association of the goal box with both a positive (food) and negative (foot shock) stimulus produced an approach-avoidance conflict (subjects exhibited "retreat behaviors" in which they would approach the goal box, stop, and then retreat back towards the start box). Once retreats were established, their sensitivity to nicotine pretreatment (0.0, 0.03, 0.045, 0.06, or 0.075 mg/kg, i.v.) was compared to saline. In subsequent tests, the effects of nicotine (0.06 or 0.03 mg/kg) were examined on spontaneous activity (locomotion) and center-square entries in an open field (anxiety). RESULTS: Doses of 0.06 and 0.075 mg/kg, but not lower doses of nicotine, reduced the number of runway retreats, and 0.06 mg/kg nicotine increased the number of open-field center entries relative to saline. No effects on locomotion were observed. CONCLUSIONS: Nicotine reduced approach-avoidance conflict and increased the rats' willingness to enter the center of an open field, suggesting that the drug can produce anxiolytic properties and that such effects may serve as an important factor in the persistence of smoking behavior.