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

Eur J Neurosci. 2007 Dec;26(12):3614-30. 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Animals
  • Anxiety / chemically induced
  • Anxiety / physiopathology*
  • Anxiety / psychology
  • Avoidance Learning / drug effects
  • Electroshock
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gastrins / metabolism*
  • In Vitro Techniques
  • Male
  • Maze Learning / drug effects
  • 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
  • gamma-Aminobutyric Acid / metabolism


  • 8-sulfocholecystokinin octapeptide
  • Excitatory Amino Acid Antagonists
  • Gastrins
  • Quinoxalines
  • Receptor, Cholecystokinin B
  • Receptors, Dopamine D1
  • Tetragastrin
  • gamma-Aminobutyric Acid
  • FG 9041
  • Sincalide