Ionotropic glutamate-receptor antagonists inhibit the aversive effects of nitric oxide donor injected into the dorsolateral periaqueductal gray of rats

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.