Lack of interaction between NMDA and cholecystokinin-2 receptor-mediated neurotransmission in the dorsolateral periaqueductal gray in the regulation of rat defensive behaviors

Several neurotransmitters, including GABA, serotonin, glutamate, and cholecystokinin, modulate defensive behaviors in the dorsolateral periaqueductal gray (dlPAG). Although both glutamate and cholecystokinin have been shown to facilitate these behaviors, a possible interaction between them remains to be examined. The present study investigates whether activation or antagonism of N-methyl-d-aspartic acid (NMDA) glutamate and cholecystokinin 2 (CCK2) receptors located in the dlPAG would interact in animals tested in the elevated T-maze. The effect of the NMDA (50 pmol) was evaluated in rats pretreated with the CCK2 receptor antagonist LY225910 (0.05 nmol). In addition, the effect of the CCK2 receptor agonist CCK-4 (0.08 nmol) was evaluated in rats pretreated with the NMDA receptor antagonist AP-7 (1.0 nmol). Intra-dlPAG injection of NMDA increased risk assessment and inhibitory avoidance behaviors. This NMDA anxiogenic-like effect was unaltered by the pretreatment with LY225910. Similarly, the shortening of escape latencies induced by CCK-4 was unaffected by AP-7. No drug changed the general exploratory activity as assessed in the open-field. These results, showing that the activation of dlPAG NMDA or CCK2 receptors facilitate anxiety- and fear-related behaviors, further implicate glutamate and cholecystokinin-mediated neurotransmission in this midbrain area on modulation of defensive behaviors. However, the regulatory action of these two excitatory neurotransmitters seems to be exerted through independent mechanisms.