Interplay between glutamate and serotonin within the dorsal periaqueductal gray modulates anxiety-related behavior of rats exposed to the elevated plus-maze

Abstract

Several neurotransmitters, including glutamate and serotonin, modulate defensive behaviors related to anxiety in the rat dorsal periaqueductal gray (PAG). Although both glutamate N-methyl- d-aspartic acid (NMDA) and serotonin type 1-A (5-HT 1A) receptors have been shown to interfere with these subtle responses, such as inhibitory avoidance, a possible interaction between them remains to be examined. To address this issue, the present study investigated whether the activation or the blockage of 5-HT 1A receptors located in the dorsal PAG would interact with NMDA function in animals exposed to the elevated plus-maze task. The effect of the NMDA (25 pmol) was evaluated in rats pretreated with the 5-HT 1A receptor antagonist WAY-100135 (2.0 or 5.0 nmol). In addition, the effect of the NMDA (100 pmol) was evaluated in rats pretreated with the 5-HT 1A receptor agonist 8-OH-DPAT (2.0 or 8.0 nmol). Intra-dorsal PAG injection of NMDA (25 pmol) increased inhibitory avoidance behavior. This anxiogenic-like effect of the NMDA was counteracted by the pretreatment with WAY-100135 (5.0 nmol). Although 100 pmol of NMDA failed to increase inhibitory avoidance in the vehicle-pretreated group, in rats pretreated with 8-OH-DPAT this NMDA dose produced an anxiogenic-like effect. These results suggest that 5-HT 1A and NMDA receptors interact in the dorsal PAG to modulate the anxiety-related behavior.