ABSTRACT
RATIONALE: Nitric oxide (NO) is a gas neurotransmitter that may facilitate glutamate release in the central nervous system. NO donors or glutamate agonists injected into the dorsolateral periaqueductal grey (dlPAG) induce flight behaviour. OBJECTIVES: To test the hypothesis that the defensive reactions induced by an NO donor in the dlPAG would be attenuated by pretreatment with AMPA/kainate or NMDA glutamate receptor antagonists. METHODS: Male Wistar rats with cannulae aimed at the dlPAG received vehicle, AP7 (a NMDA receptor antagonist, 2 nmol) or NBQX (an AMPA/kainite receptor antagonist, 100 nmol) injection 10 min before the administration of SIN-1 (an NO donor, 300 nmol). Immediately after the last injection, their behavior was observed in an open arena during 10 min. RESULTS: SIN-1 induced flight reactions characterized by running and jumps. Pretreatment with AP7 or NBQX completely prevented the effects of SIN-1. CONCLUSION: The results suggest that the aversive reactions induced by an NO donor in the dlPAG depend on ionotropic glutamate receptor activation.
Subject(s)
2-Amino-5-phosphonovalerate/analogs & derivatives , Excitatory Amino Acid Antagonists/pharmacology , Motor Activity/drug effects , Nitric Oxide Donors/pharmacology , Periaqueductal Gray/drug effects , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Male , Molsidomine/analogs & derivatives , Molsidomine/pharmacology , Nitric Oxide/metabolism , Periaqueductal Gray/metabolism , Rats , Rats, Wistar , Receptors, AMPA/agonists , Receptors, AMPA/antagonists & inhibitors , Receptors, Kainic Acid/agonists , Receptors, Kainic Acid/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/agonists , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Time FactorsABSTRACT
The dorsolateral periaqueductal grey (dlPAG) is proposed to play a role in the elaboration of defensive behaviors. Nitric oxide (NO) donors, injected into this region, induce flight reactions. The reactions have also been observed after electrical or chemical stimulation of the inferior colliculus (IC). The enzyme responsible for NO formation, neuronal nitric oxide synthase (nNOS), is expressed in the IC. The aims of this study were to investigate if NO donors injected into the IC would also cause aversive reactions and if these reactions would involve activation of NMDA receptors. The results showed that 3-morpholinosylnomine hydrochloride (SIN-1; 300 nmol), an NO donor, injected into the central nucleus but not into the dorsal cortex of the IC (CIC and DCIC, respectively) of male Wistar rats induced flight reactions characterized by galloping and jumps. Pretreatment (10 min) with methylene blue (MB; 100 or 200 nmol), a guanylate cyclase (GC) inhibitor, partially inhibited this flight reaction, decreasing the number of jumps. 8-Bromo-cGMP (8-Br-GMP), a membrane-permeable cGMP analogue, increased the number of contralateral turnings. Pretreatment (10 min) with the NMDA receptor antagonist amino-7-phosphonoheptanoic acid (AP7; 2 nmol) completely prevented the effects of SIN-1. It is concluded that NO may induce aversive reactions in the CIC and that these reactions depend on NMDA receptor activation. They may also partially involve facilitation of GC activity.
