U-69,593 microinjection in the infralimbic cortex reduces anxiety and enhances spontaneous alternation memory in mice

The present report investigated the contributions of the ventromedial prefr ontal cortex to the control of spontaneous alternation/working memory and a nxiety-related behaviour. In Experiment 1, we examined the effects of micro injections of the selective kappa, receptor agonist, U-69,593, in the infra limbic cortex (IL) of CD-1 mice on several ethologically-derived anxiety in dices in the elevated plus-maze (EPM) and defensive/withdrawal (D/W) anxiet y in the open field, as well as on memory in the EPM transfer-latency (T-L) test and implicit spontaneous alternation memory (SAP) in the Y-maze. In w eek 1, pretreatment with one injection of vehicle, 1, 10 or 25 nmol/1.0 mu l U-69,593 in the IL dose-dependently prolonged T-L and produced a dose-dep endent anxiolytic behavioural profile in the first EPM trial. Following a 2 4-h delay, the same mice were given a drug-free second trial in the EPM tes ts of T-L memory and anxiety. Whereas T-L memory was not disturbed, small b ut detectable carry-over effects were observed in trial-2 EPM behaviour rel ative to vehicle-treated animals. In week 2, the same groups of mice were a gain pretreated with one injection of the same doses of U-69,593 in the IL and given a D/W test in an open field, followed immediately by an 8-min SAP trial in the Y-maze. The smallest U-69,593 dose was anxiolytic in the D/W test, and SAP/working memory was dose-dependently enhanced in the Y-maze. I n Experiment 2, we evaluated whether 0.5 mu l volume microinjections would produce comparable behavioural and carry-over effects in the IL of three ne w groups of CD-1 mice, in the event that the 1.0 mu l volume injections use d in Experiment 1 diffused beyond the IL and therefore may have confounded some effects. Experiment 2 procedures were carried out in the same manner a s in Experiment 1, except the animals were tested in reverse order. Thus in week 1, SAP memory was tested in the Y-maze followed by D/W anxiety in the open field for half of the animals in each group, and the other half was t ested in reverse order. In week 2, T/L memory and anxiety were tested in th e EPM in 2 trials as described in Experiment I. Pretreatment with one injec tion of vehicle, 10 or 25 nmol/0.5 mu l U-69,593 in the IL reduced D/W anxi ety and enhanced SAP memory regardless of testing order in week 1. In week 2, the same groups of mice were again pretreated with one injection of the same doses of U-69,593 in 0.5 mu l volumes in the IL and tested in the EPM. In a similar fashion to Experiment I, U-69,593 dose-dependently prolonged T/L and produced an anxiolytic behavioural profile in the first EPM trial. Following a 24-h delay, T/L recall memory was again not significantly influ enced, but a robust anxiolytic behavioural profile was observed in the seco nd drug-free anxiety vial in the EPM relative to vehicle-treated animals. R esults are discussed relative to a) injection volumes and testing order, b) the possible influence kappa receptors may exert on neurochemical responsi vity to anxiety-provoking environments in the IL area of the mPFC, c) the p ossibility that kappa-mediated anxiolysis from the IL in CD-1 mice results from interactions with neurochemical systems involved in the blunting of in coming anxiety-provoking information, d) evidence that SAP memory may be an implicit subtype of working memory, and e) the possibility that VL implici t working memory processes may modulate the induction and expression of anx iety-related behaviour. (C) 2000 Elsevier Science B.V. All rights reserved.