tetragastrin and 2-amino-7-phosphonoheptanoic-acid

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 (CCK(2)) 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 CCK(2) receptor antagonist LY225910 (0.05 nmol). In addition, the effect of the CCK(2) 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 CCK(2) 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.

Topics: 2-Amino-5-phosphonovalerate; Animals; Behavior, Animal; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Gastrointestinal Agents; Male; Maze Learning; N-Methylaspartate; Periaqueductal Gray; Quinazolinones; Rats; Rats, Wistar; Receptor, Cholecystokinin B; Signal Transduction; Tetragastrin