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-1 mice. Specifically, pretrial microinjection of the kappa(1) 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 working memory in the Y-maze. In the present study we sought to determine whether these effects were specific to IL kappa receptors. We hypothesized that microinjection of the kappa antagonist, norBNI, in the IL cortex would influence anxiety and spontaneous memory in an opposite direction to the effects produced by the kappa(1) agonist. In week 1, transfer-latency reference memory and anxiety were tested in the elevated plus-maze in two separate trials with an intertrial interval of 24 h. In week 2, spontaneous working memory 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 the other half was tested in reverse order. Pretreatment with one injection of vehicle, 1, 5 or 10 nmol/0.5 microl norBNI in the IL cortex dose-dependently reduced transfer-latencies and produced an anxiogenic behavioural profile in the first elevated plus-maze trial. Following a 24 h delay, transfer-latency reference memory was not influenced, but a robust anxiogenic behavioural profile was observed in the second no-injection anxiety trial in the elevated 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 pretreatment was anxiogenic in the defensive/withdrawal anxiety test and disrupted spontaneous working memory regardless of testing order. The present results show the influence of kappa receptor modulation on anxiety induction and spontaneous working memory. These results also support the hypothesis that immediate memory processing may modulate the induction of anxiety-related behaviours.

Pubmed ID: 10762693 RIS Download