Role of cholecystokinin-A and cholecystokinin-B receptors in anxiety

Abstract

Evidence from several laboratories indicates that the anxiogenic effects of cholecystokinin (CCK) are mediated by CCKB receptors. However, it has been reported that CCKA receptors have been found in brain and CCKA antagonists have anxiolytic properties. The aim of this work was to study whether CCKA receptors are also involved in the modulation of anxiety. Anxiogenic effects were observed in the elevated plus maze in rats when pure CCKB receptor agonists (CCK-4 and CCK-8 non-sulfated) or CCK-8S, a CCKB/CCKA agonist, were injected into the lateral ventricle. In contrast, CCK-33, a CCKA agonist or CCK-(1-21) and CCK-(26-29) were ineffective. Furthermore, the anxiogenic effects of CCK-8S were prevented by blocking CCKB but not CCKA receptors. Finally, CCK-33 injected into the postero-medial nucleus accumbens failed to affect the anxiety level of the rats. These results indicate that CCKA receptors are not involved in anxiety, as measured by the paradigms used in this work.

Interaction between the Cholecystokinin and Endogenous Cannabinoid Systems in Cued Fear Expression and Extinction Retention

“…Although some studies show an anxiolytic effect of CCKBR antagonists and CCKBR knockout (Matto et al, 1997, Revel et al, 1998, Tsutsumi et al, 1999, Abramov et al, 2008, others report null results Rodgers, 1996, Griebel et al, 1997). Still, others report that CCKBR antagonists only have anxiolytic effects when coadministered with CCK (Hernandez-Gomez et al, 2002). The mixed conclusions of the literature suggest that CCKBR likely has a role in anxiety-like behavior, but that the CCK system might be particularly sensitive to environmental conditions, prior stress, and/or specific testing parameters.…”

Anxiogenic Effect of Cholecystokinin in the Dorsal Periaqueductal Gray

“…Similar effects have been reported after i.c.v. administration of CCK-8s (Hernandez-Gomez et al, 2002). CCK-2 receptors are abundantly expressed in the brain and are present in the PAG (Mercer et al, 1996).…”

“…Cholecystokinin (CCK) is one of the most widespread peptide system in the brain. It is involved in many brain physiological or pathological conditions, including anxiety, panic, and depression (Guimarães et al, 1992;Hernandez-Gomez et al, 2002;Bradwejn et al, 1992Bradwejn et al, , 1994Rehfeld, 2000). CCK-immunoreactive fibers and a high concentration of CCK exist in the PAG (De Belleroche et al, 1990;Liu et al, 1994).…”

“…Aversive stimuli such as restraint, social isolation, or exposure to the smell of a predator increase CCK levels and/or expression in the PAG and limbic regions such as the amygdala and hippocampus (Del Bel and Guimarães, 1997;Pavlasevic et al, 1993;Rosen et al, 1992). Systemic injection of CCK agonists or antagonists produces anxiogenic or anxiolytic effects, respectively (Griebel et al, 1997, Hernandez-Gomez et al, 2002. These effects may involve the dPAG since systemic administration of anxiogenic compounds, including the CCK analogue BOC-CCK4, induces Fos immunoreactivity in the dPAG (Singewald and Sharp, 2000).…”

Targeted invalidation of CCK2 receptor gene induces anxiolytic-like action in light–dark exploration, but not in fear conditioning test

“…CCK receptor agonists inhibit exploratory behaviour of mice and rats in the elevated plus-maze test, decrease the time spent and exploratory activity in the light compartment of the light-dark compartment test, and support acquisition and retention in fear-motivated tests Shlik et al 1997). The anxiogenic-like action of CCK agonists is mediated via CCK 2 receptors (Shlik et al 1997;Nobel et al 1999;Hernandez-Gomez et al 2002). Also, rats selected according to their anxiety-like behaviour in the elevated plus-maze display an increased density of CCK 2 receptors in the forebrain structures compared to animals having reduced anxiety (Kõks et al 1997).…”