Modulation of behaviour on trials 1 and 2 in the elevated plus-maze test of anxiety after systemic and hippocampal administration of nicotine

Rationale: The elevated plus-maze provides a test situation in which distin ctive states of anxiety are elicited on trials 1 and 2 and the dorsal hippo campus has previously been shown to mediate the anxiogenic effects of (-)-n icotine in the social interaction test. Objective: To determine the effects of a wide dose range of (-)-nicotine on trial 1 and 2 in the plus-maze aft er systemic administration and whether the dorsal hippocampus is a site med iating the anxiogenic effect of nicotine. Methods: (-)-Nicotine (0.001, 0.0 05, 0.01, 0.05, 0.1, 0.5 and 1 mg/kg) was injected IP 30 min before testing for 5 min in the plus-maze. Rats receiving dorsal hippocampal infusions re ceived bilateral infusions of 0.5 mu l of artificial CSF or (-)-nicotine (0 .1, 1, 4 or 8 mu g). The needle was left in place for 50 s after injection and testing took place 3 min later. Rats tested on trial 1 were naive to th e plus-maze those tested on trial 2 had received a previous 5-min undrugged exposure to the maze 48 h earlier. Results: Low doses of (-)-nicotine (0.0 01, 0.005, 0.01, 0.05 and 0.1 mg/kg, IF) were without effect on either tria l, but higher doses (0.5 and 1 mg/kg, LP) had anxiogenic effects on both tr ials, as shown by decreases in percentage time spent and percentage entries onto the open arms. Infusion of (-)-nicotine (0.1, 1,3 and 8 mu g) bilater ally into the dorsal hippocampus was without effect on trial 1, but 1 mu g had an anxiolytic effect on trial 2, shown by an increased percentage time spent on the open arms. Conclusions: The results on both trials in the plus -maze after systemic administration of nicotine add to previous reports fro m the social interaction test that high doses of nicotine have anxiogenic e ffects. However, the effects of nicotine in the dorsal hippocampus are diff erent in all three anxiety tests (anxiogenic in social interaction, ineffec tive on trial 1, anxiolytic on trial 3) showing that nicotinic cholinergic control in this brain region may vary depending on the state and/or type of anxiety generated by the test. The brain region(s) underlying the anxiogen ic effects of IP nicotine on both trials in the plus-maze remain to be iden tified.