Role of the amygdaloid cholecystokinin (CCK)/gastrin-2 receptors and terminal networks in the modulation of anxiety in the rat. Effects of CCK-4 and CCK-8S on anxiety-like behaviour and [3H]GABA release.
The amygdala plays a key role in fear and anxiety. The intercalated islands are clusters of glutamate-responsive GABAergic neurons rich in cholecystokinin (CCK)-2 receptors which control the trafficking of nerve impulses from the cerebral cortex to the central nucleus of amygdala. In this study, the nature of the CCK-glutamate-GABA interactions within the rat rostral amygdala, and their relevance for anxiety, were studied. CCK/gastrin-like immunoreactive nerve terminals were found to be mainly restricted to the paracapsular intercalated islands and the rostrolateral part of the main intercalated island. Behaviourally, the bilateral microinjection of CCK-4 (0.043-4.3 pmol/side) or CCK-8S (4.3 pmol/side) into the rostrolateral amygdala reduced the open-arm exploration in the elevated plus-maze without affecting locomotion. In contrast, neither CCK-4 nor CCK-8S (0.043-4.3 pmol/side) had any effects in the shock-probe burying test as compared with their saline-treated controls. Biochemically, CCK-4 (0.3 and 1.5 microm), unlike CCK-8S, enhanced significantly the K(+)-stimulated release of [(3)H]GABA from amygdala slices. These effects were fully prevented by prior superfusion of the slices with either the selective CCK-2 receptor antagonist CR2945 (3 microm), or 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX), 10 microm, a glutamatergic (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist. It is suggested that CCK modulates glutamate-GABA mechanisms by acting on CCK-2 receptors via volume transmission occurring at the level of the basolateral amygdaloid nucleus and/or by synaptic or perisynaptic volume transmission in the region of the rostrolateral main and paracapsular intercalated islands, resulting in subsequent disinhibition of the central amygdaloid nucleus and anxiety or panic-like behaviour.
Pérez de la Mora
Miguel
M
Department of Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-253, México 04510 DF, México. mperez@ifc.unam.mx
Hernández-Gómez
Ana María
AM
Arizmendi-García
Yexel
Y
Jacobsen
Kirsten X
KX
Lara-García
Daniel
D
Flores-Gracia
Candy
C
Crespo-Ramírez
Minerva
M
Gallegos-Cari
Andrea
A
Nuche-Bricaire
Avril
A
Fuxe
Kjell
K
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects; D004597:Electroshock; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005755:Gastrins / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009411:Nerve Endings / Q000503:physiopathology*; D009415:Nerve Net / Q000503:physiopathology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D012844:Sincalide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D013758:Tetragastrin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C090019:8-sulfocholecystokinin octapeptide; D018691:Excitatory Amino Acid Antagonists; D005755:Gastrins; D011810:Quinoxalines; D043887:Receptor, Cholecystokinin B; D017447:Receptors, Dopamine D1; D013758:Tetragastrin; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; D012844:Sincalide