The expression of contextual fear conditioning involves activation of an NMDA receptor-nitric oxide pathway in the medial prefrontal cortex

The ventral portion of medial prefrontal cortex (vMPFC) is involved in contextual fear-conditioning expression in rats. In the present study, we investigated the role of local N-methyl-D-aspartic acid (NMDA) glutamate receptors and nitric oxide (NO) in vMPFC on the behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats exposed to a context fear conditioning. The results showed that both freezing and cardiovascular responses to contextual fear conditioning were reduced by bilateral administration of NMDA receptor antagonist LY235959 (4 nmol/200 nL) into the vMPFC before reexposition to conditioned chamber. Bilateral inhibition of neuronal NO synthase (nNOS) by local vMPFC administration of the N omega-propyl-L-arginine (N-propyl, 0.04 nmol/200 nL) or the NO scavenger carboxy-PTI0 (1 nmol/200 A) caused similar results, inhibiting the fear responses. We also investigated the effects of inhibiting glutamate- and NO-mediated neurotransmission in the vMPFC at the time of aversive context exposure on reexposure to the same context. It was observed that the 1st exposure results in a significant attenuation of the fear responses on reexposure in vehicle-treated animals, which was not modified by the drugs. The present results suggest that a vMPFC NMDA-NO pathway may play an important role on expression of contextual fear conditioning.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)[151931/2005-4

Effects of bilateral microinjection of 200 nL of vehicle, 4 nmol of LY235959 (LY), or 0

04 nmol of N-propyl in the percentage of time spent in freezing behavior of fear-conditioned rats ( = 5/group) 10 min before the 1st reexposition of context (day 1) and 6 days before the 2nd reexposition to context (day 7). Columns represent the mean and bars the SEM, * < 0.05, compared with vehicle-conditioned group in day 1.<p><b>Copyright information:</b></p><p>Taken from "The Expression of Contextual Fear Conditioning Involves Activation of an NMDA Receptor–Nitric Oxide Pathway in the Medial Prefrontal Cortex"</p><p></p><p>Cerebral Cortex (New York, NY) 2007;18(9):2027-2035.</p><p>Published online 24 Dec 2007</p><p>PMCID:PMC2517108.</p><p></p

Cardiovascular effects of acetylcholine microinjection into the ventrolateral and dorsal periaqueductal gray of rats

In the present study, we describe the cardiovascular effects of local acetylcholine (Ach) microinjection into both the ventrolateral (vlPAG) and dorsal (dPAG) periaqueductal gray areas of anesthetized rats and the possible local receptors involved with these responses. Microinjection of Ach (9, 27, 45 or 81 nmol/50 nL) into the vlPAG caused dose-related depressor responses. These hypotensive responses were blocked by local pretreatment with increasing doses of the nonselective muscarinic antagonist atropine (1, 3 or 9 nmol/50 nL). The microinjection of Ach into the dPAG caused no significant cardiovascular responses in anesthetized rats. In conclusion, the present findings suggest that a cholinergic system present in the vlPAG, but not in the dPAG, is involved with cardiovascular system control. Moreover, these cardiovascular responses evoked by Ach are mediated by muscarinic receptors. (C) 2010 Elsevier B.V. All rights reserved

Time course of the effects of bilateral microinjection of 200 nL of vehicle, 4 nmol of LY235959 (LY), 4 nmol of NBQX, 0

04 nmol of N-propyl, or 1 nmol of c-PTIO in the mean arterial pressure (ΔMAP) and heart rate (ΔHR) recorded in nonconditioned and fear-conditioned rats ( = 5/group). Asterisk indicates significant treatment effect ( < 0.05) compared with vehicle- and NBQX-treated animals. Further specifications as in .<p><b>Copyright information:</b></p><p>Taken from "The Expression of Contextual Fear Conditioning Involves Activation of an NMDA Receptor–Nitric Oxide Pathway in the Medial Prefrontal Cortex"</p><p></p><p>Cerebral Cortex (New York, NY) 2007;18(9):2027-2035.</p><p>Published online 24 Dec 2007</p><p>PMCID:PMC2517108.</p><p></p

Panicolytic-like effect of BDNF in the rat dorsal periaqueductal grey matter: the role of 5-HT and GABA

A wealth of evidence suggests a role for brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) in the aetiology of depression and in the mode of action of antidepressant drugs. Less clear is the involvement of this neurotrophin in other stress-related pathologies such as anxiety disorders. The dorsal periaqueductal grey matter (DPAG), a midbrain area rich in BDNF and TrkB receptor mRNAs and proteins, has been considered a key structure in the pathophysiology of panic disorder. In this study we investigated the effect of intra-DPAG injection of BDNF in a proposed animal model of panic: the escape response evoked by the electrical stimulation of the same midbrain area. To this end, the intensity of electrical current that needed to be applied to DPAG to evoke escape behaviour was measured before and after microinjection of BDNF. We also assessed whether 5-HT- or GABA-related mechanisms may account for the putative behavioural/autonomic effects of the neurotrophin. BDNF (0.05, 0.1, 0.2 ng) dose-dependently inhibited escape performance, suggesting a panicolytic-like effect. Local microinjection of K252a, an antagonist of TrkB receptors, or bicuculline, a GABA(A) receptor antagonist, blocked this effect. Intra-DPAG administration of WAY-100635 or ketanserin, respectively 5-HT(1A) and 5-HT(2A/2c) receptor antagonists, did not alter BDNF`s effects on escape. Bicuculline also blocked the inhibitory effect of BDNF on mean arterial pressure increase caused by electrical stimulation of DPAG. Therefore, in the DPAG, BDNF-TrkB signalling interacts with the GABAergic system to cause a panicolytic-like effect.FAPESPCNPq, Brazi