Journal of Behavioral and Brain Science, 2011, 1, 181-187 doi:10.4236/jbbs.2011.13024 Published Online August 2011 (http://www.SciRP.org/journal/jbbs) Copyright © 2011 SciRes. JBBS Anxiety-Behavior Modulated by Ventral Medial Prefrontal Cortex of Rats Submitted to the Vogel Conflict Test Involves a Local NMDA Receptor and Nitric Oxide Sabrina F. Lisboa, Francisco S. Guimarães, Leonardo B. M. Resstel * Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil E-mail: * leoresstel@yahoo.com.br Received March 30, 2011; revised April 18, 2011; accepted April 25, 2011 Abstract 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 micro- injected 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-be- havior in the VCT by control punished behavior. Moreover, this NO modulation could be associated with local glutamatergic activation through NMDA receptors. Keywords: Infra Limbic Cortex, Prelimbic Cortex, Anxiolytic-Like Effects, Defensive Behavior 1. Introduction The medial prefrontal cortex (MPFC) of rats has been the focus of considerable studies, owing in part to under- standing the central importance of its dysfunction in a wide array of psychopathological conditions in humans [1-3]. In rats, the MPFC is activated by exposure to a vari- ety of anxiety provoking challenges, and can be blocked by anxiolytic benzodiazepine [4-8]. Moreover, in rodents the MPFC presents an important role on neuroendocrine, autonomic and behavioral modulation during defense reactions [6,9-11]. The ventral portion of the MPFC (vMPFC), which is composed of prelimbic cortex (PL) and infralimbic cor- tex (IL) [10], is particularly responsive to threat stimuli and the inhibition of its neurotransmission induces anx- iolytic-like effect accompanied by attenuated cardiovas- cular activity in a model of contextual fear conditioning [4,10,12,13]. These data show the specific importance of local vMPFC neurotransmission in responses evoked by anxiety behavior in animal model. The Vogel conflict test (VCT) is an animal model used to study the anxiety response based on suppression of punished responses, when water-deprived rats are ex- posed to the conflict between licking the spout of a bottle and receiving a mild shock on the tong [14-16]. Anxio- lytic drugs, such as the benzodiazepines, are able to in- crease the number of punished licks [14,15]. Moreover, it has recently described that local vMPFC neurotransmis- sion is involved with anxiety-like behavior response ob- served in VCT [17]. It has been described that during defensive reactions,