Abstract
BackgroundSeveral studies had demonstrated the involvement of the dorsolateral portion of periaqueductal grey matter (dlPAG) in defensive responses. This region contains a significant number of neurons containing the enzyme nitric oxide synthase (NOS) and previous studies showed that non-selective NOS inhibition or glutamate NMDA-receptor antagonism in the dlPAG caused anxiolytic-like effects in the elevated plus maze.MethodsIn the present study we verified if the NMDA/NO pathway in the dlPAG would also involve in the behavioral suppression observed in rats submitted to the Vogel conflict test. In addition, the involvement of this pathway was investigated by using a selective nNOS inhibitor, Nω-propyl-L-arginine (N-Propyl, 0.08 nmol/200 nL), a NO scavenger, carboxy-PTIO (c-PTIO, 2 nmol/200 nL) and a specific NMDA receptor antagonist, LY235959 (4 nmol/200 nL).ResultsIntra-dlPAG microinjection of these drugs increased the number of punished licks without changing the number of unpunished licks or nociceptive threshold, as measure by the tail flick test.ConclusionThe results indicate that activation of NMDA receptors and increased production of NO in the dlPAG are involved in the anxiety behavior displayed by rats in the VCT.
Highlights
Several studies had demonstrated the involvement of the dorsolateral portion of periaqueductal grey matter in defensive responses
Glutamate-NMDA receptor activation can induce the production of nitric oxide (NO) by activation of a calmodulin-dependent enzyme, the neuronal isoform of the nitric oxide synthase, present in several corticolimbic structures [11,12]. nNOS inhibition promotes effects similar to those observed after NMDA antagonism [13,14]
The Vogel conflict test In the first experiment, the animals that had received LY235959 (n = 8), N-propyl (n = 7) or c-PTIO (n = 9) into the dorsolateral portion of periaqueductal grey matter (dlPAG) showed an increased the number of punished licks in the Vogel conflict test as compared to animals which had received vehicle (n = 10, F6,57= 6.71; P < 0.01, Figure 2)
Summary
Several studies had demonstrated the involvement of the dorsolateral portion of periaqueductal grey matter (dlPAG) in defensive responses This region contains a significant number of neurons containing the enzyme nitric oxide synthase (NOS) and previous studies showed that non-selective NOS inhibition or glutamate NMDA-receptor antagonism in the dlPAG caused anxiolytic-like effects in the elevated plus maze. Antagonism of NMDA receptors AP7 in the dlPAG causes an anxiolytic-like effect in rats submitted to the elevated plus maze and Vogel conflict test [8,9,10]. These data indicate that glutamate receptors in the dlPAG play an important role in defensive responses. Though, to investigate drug effects in a specific brain site using different tests of anxiety
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