Tolerance to nicotine's effects in the elevated plus-maze and increased anxiety during withdrawal

In the elevated plus-maze test of anxiety, nicotine (0.1 mg/kg sc; 30 min a fter injection) had a significant anxiogenic effect, shown by specific decr eases in the percentage of time spent on the open arms and in the percentag e of open-arm entries. Tolerance developed to this anxiogenic effect after 7 days of nicotine treatment (0.1 mg/kg/day). Five minutes after an acute i njection, nicotine (0.1 mg/kg) was ineffective, but after 7 days of treatme nt a significant anxiolytic effect, shown by specific increases in the perc entage of time spent on the open arms and in the percentage of open-arm ent ries, emerged. After 14 days of nicotine treatment, tolerance developed to this anxiolytic effect. There was a complete dissociation between the effec ts of nicotine on the measures of anxiety, and on the locomotor activity as measured by closed-arm entries. No changes in closed-arm entries were foun d after acute administration of nicotine, but rats tested 30 min after thei r 7th injection made significantly fewer, and those tested 5 min after thei r 14th injection made significantly more, entries than their respective con trols. Rats that were tested after 24 h withdrawal from six daily nicotine injections showed a significant anxiogenic effect. A low dose of nicotine ( 5 ng) injected into the dorsal hippocampus was without effect in vehicle pr etreated rats, but it was able to reverse the anxiogenic effect found after 24 h of withdrawal from 6 days of nicotine treatment. (C) 2001 Elsevier Sc ience Inc. All rights reserved.