Concurrent modulation of anxiety and memory

We have previously shown that the ventromedial prefrontal cortex (vmPFC) is involved in spontaneous working memory and anxiety-related behaviour in CD -I mice, specifically, pretrial microinjection of the kappa, agonist, U-69, 593, in the infralimbic (IL) area of the vmPFC produced a robust anxiolytic behavioural profile in the elevated plus-maze and enhanced spontaneous wor king memory in the Y-maze. In the present study we sought to determine whet her these effects were specific to IL kappa receptors. We hypothesized that microinjection of the kappa antagonist, norBNI, in the IL cortex would inf luence anxiety and spontaneous memory in an opposite direction to the effec ts produced by the kappa(1) agonist. In week I, transfer-latency reference memory and anxiety were tested in the elevated plus-maze in two separate tr ials with an intertrial interval of 24 h. In week 2, spontaneous working me mory was tested in the Y-maze followed immediately by defensive/withdrawal anxiety in the open field for one half of the animals in each group, and th e other half was tested in reverse order. Pretreatment with one injection o f vehicle, 1, 5 or 10 nmol/0.5 mu l norBNI in the IL cortex dose-dependentl y reduced transfer-latencies and produced an anxiogenic behavioural profile in the first elevated plus-maze trial. Following a 24 h delay, transfer-la tency reference memory was not influenced, but a robust anxiogenic behaviou ral profile was observed in the second no-injection anxiety trial in the el evated plus-maze relative to control animals. In week 2, the same groups of mice were again pretreated with one injection of the same doses of norBNI in the IL cortex and tested in the open field and Y-maze. NorBNI pretreatme nt was anxiogenic in the defensive/withdrawal anxiety test and disrupted sp ontaneous working memory regardless of testing order. The present results s how the influence of kappa receptor modulation on anxiety induction and spo ntaneous working memory. These results also support the hypothesis that imm ediate memory processing may modulate the induction of anxiety-related beha viours. (C) 2000 Elsevier Science B.V. AU rights reserved.