title: Lack of interaction between NMDA and cholecystokinin-2 receptor-mediated neurotransmission in the dorsolateral periaqueductal gray in the regulation of rat defensive behaviors.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil. lejobe@usp.br
authors.forename: L J
authors.initials: LJ
authors.lastname: Bertoglio
authors.forename: F S
authors.initials: FS
authors.lastname: Guimarães
authors.forename: H
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000378:metabolism*; D052999:Quinazolinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013758:Tetragastrin / Q000494:pharmacology
chemical_list: C435663:2-(2-(5-bromo-1H-indol-3-yl)ethyl)-3-(1-methylethoxyphenyl)-4-(3H)-quinazolinone; D018690:Excitatory Amino Acid Agonists; D005765:Gastrointestinal Agents; D052999:Quinazolinones; D043887:Receptor, Cholecystokinin B; D013758:Tetragastrin; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid