Anxiety-Behavior Modulated by Ventral Medial Prefrontal Cortex of Rats Submitted to the Vogel Conflict Test Involves a Local NMDA Receptor and Nitric Oxide

It was demonstrated in the Vogel conflict test (VCT) that the ventral portion of medial prefrontal cortex (vMPFC) of rats is involved with anxiety behavior. Moreover, the vMPFC local glutamatergic and nitrergic system interaction is involved in modulation of fear conditioning, a model of anxiety. To better understand the role of the MPFC-glutamatergic and nitrergic system on the VTC behavior response, male Wistar rats (250 g) were water deprived for 48 h before the VCT. After 24 h of water deprivation, they were subjected to an initial 3-min non-punished (pre-test) drinking session. Twenty-four hours later bilateral microinjections of NMDA-antagonist LY235959 (4 nmol/200 nL), the specific nNOS inhibitor N-Propyl-L-arginine (N-Propyl –0.08 nmol/200 nL), the NO scavenger Carboxi-PTIO (C-PTIO, 2 nmol/200 nL) or 200nL of vehicle were applied in the vMPFC. After 10 min, the animals were submitted to 3-min punished-licking session. LY235959 increased the number of punished licks. Similar to LY235959, both N-Propyl and C-PTIO also increased the number of punished licks. No changes were observed when LY235959, N-Propyl and C-PTIO were microinjected into vMPFC surrounding structures such as the cingulate cortex area 1, the corpus callosum and the tenia tecta. In control experiments these drugs did not change neither the number of unpunished licks nor had any effect in the tail-flick test. The results show that NO signaling in the vMPFC can modulate anxiety-behavior in the VCT by control punished behavior. Moreover, this NO modulation could be associated with local glutamatergic activation through NMDA receptors.