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

• Published in: The European journal of neuroscience 2007-12, Vol.26 (12), p.3614-3630
• Main Authors: Pérez de la Mora, Miguel, Hernández-Gómez, Ana María, Arizmendi-García, Yexel, Jacobsen, Kirsten X., Lara-García, Daniel, Flores-Gracia, Candy, Crespo-Ramírez, Minerva, Gallegos-Cari, Andrea, Nuche-Bricaire, Avril, Fuxe, Kjell
• Format: Article
• Language: English
• Subjects: amygdala; Amygdala - drug effects; Amygdala - metabolism; Animals; Anxiety - chemically induced; Anxiety - physiopathology; Anxiety - psychology; Avoidance Learning - drug effects; basolateral amygdaloid nucleus; Electroshock; Excitatory Amino Acid Antagonists - pharmacology; gamma-Aminobutyric Acid - metabolism; Gastrins - metabolism; glutamate; In Vitro Techniques; intercalated islands; Male; Maze Learning - drug effects; Medicin och hälsovetenskap; Microinjections; Motor Activity - drug effects; Nerve Endings - physiopathology; Nerve Net - physiopathology; Quinoxalines - pharmacology; Rats; Rats, Wistar; Receptor, Cholecystokinin B - metabolism; Receptors, Dopamine D1 - metabolism; Sincalide - administration & dosage; Sincalide - analogs & derivatives; Sincalide - pharmacology; Tetragastrin - administration & dosage; Tetragastrin - antagonists & inhibitors; Tetragastrin - pharmacology
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/j.1460-9568.2007.05963.x

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 µm), unlike CCK‐8S, enhanced significantly the K+‐stimulated release of [3H]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 µm), or 6,7‐dinitroquinoxaline‐2,3(1H,4H)‐dione (DNQX), 10 µm, a glutamatergic (+/–)‐α‐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.