‘Anxiolytic’ effect of CCK-antagonists on plus-maze behavior in mice

Rataud, J.; Darche, F.; Piot, O.; Stutzmann, Jean‐Marie; Böhme, Georg Andrees; Blanchard, Jean‐Charles

doi:10.1016/0006-8993(91)91139-r

Cited by 70 publications

(21 citation statements)

References 11 publications

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“…The reversal by the CCK-A receptor antagonist was observed under conditions that did not influence basal food intake as reported previously (18,32). It is also unlikely to represent the anxiolytic-like effect of devazepide because L-365,260, which has established anxiolytic-like properties in mice (43,44), did not influence the food-suppressing effect of leptin-CCK. These results indicate that the CCK-A receptor subtype is critical for leptin-CCK-induced food intake suppression as established previously for the satiating effect of peripherally administered CCK alone (14,18,45,46).…”

Section: Discussionsupporting

confidence: 75%

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Barrachina

Martı́nez

Wang

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

405

256

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Leptin is a circulating protein involved in the long-term regulation of food intake and body weight. Cholecystokinin (CCK) is released postprandially and elicits satiety signals. We investigated the interaction between leptin and CCK-8 in the short-term regulation of food intake induced by 24-hr fasting in lean mice. Leptin, injected intraperitoneally (i.p.) at low doses (4-120 g͞kg), which did not influence feeding behavior for the first 3 hr postinjection, decreased food intake dose dependently by 47-83% during the first hour when coinjected with a subthreshold dose of CCK. Such an interaction was not observed between leptin and bombesin. The food-reducing effect of leptin injected with CCK was not associated with alterations in gastric emptying or locomotor behavior. Leptin-CCK action was blocked by systemic capsaicin at a dose inducing functional ablation of sensory afferent fibers and by devazepide, a CCK-A receptor antagonist but not by the CCK-B receptor antagonist, L-365,260. The decrease in food intake which occurs 5 hr after i.p. injection of leptin alone was also blunted by devazepide. Coinjection of leptin and CCK enhanced the number of Fos-positive cells in the hypothalamic paraventricular nucleus by 60%, whereas leptin or CCK alone did not modify Fos expression. These results indicate the existence of a functional synergistic interaction between leptin and CCK leading to early suppression of food intake which involves CCK-A receptors and capsaicin-sensitive afferent fibers.

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Section: Discussionsupporting

confidence: 75%

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Barrachina

Martı́nez

Wang

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

405

256

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“…Conversely, systemic administration of the CCK B receptor antagonist L-365,260 attenuates fear-potentiated startle in rats (Josselyn et al, 1995a). These results are consistent with the anxiogenic and anxiolytic effects of systemically administered CCK B agonists and antagonists, respectively, in a range of behavioral paradigms including the elevated plus maze, light-dark box, punished responding, and social interaction (see, for example, Hughes et al, 1990;Harro and Vasar, 1991;Rataud et al, 1991;Singh et al, 1991;Männistö et al, 1994;Rex et al, 1994). These studies suggest that CCK B receptors mediate a constellation of behaviors associated with "anxiety" (see, for example, Harro et al, 1993).…”

supporting

confidence: 67%

Activation of Amygdala Cholecystokinin_BReceptors Potentiates the Acoustic Startle Response in the Rat

Frankland

Josselyn

Bradwejn³

et al. 1997

J. Neurosci.

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The acoustic startle reflex is a sensitive index of "anxiety" and "fear." Potentiation of startle by conditioned and unconditioned fear stimuli appears to be mediated by the amygdala. Cholecystokinin B (CCK B ) agonists increase "anxiety" in laboratory animals and induce "panic" in humans. Here, we investigate the role CCK B receptor-mediated mechanisms in the amygdala in the potentiation of startle. First, intra-amygdala infusions of the CCK B receptor agonist pentagastrin (0, 0.01, 0.1, 1, and 10 nM) produced a dose-related potentiation of acoustic startle responses. At the highest dose, startle amplitudes were increased up to 90% above preinfusion baseline levels. Second, similar infusions of pentagastrin had no effect on locomotor activity over the same time course, showing that increases in startle responsivity after infusions of pentagastrin are not attributable to nonspecific changes in motor activity. Third, infusions of similar doses of pentagastrin into the striatum or nucleus accumbens did not potentiate startle responses. Fourth, pretreatment with the CCK B receptor antagonist L-365,260 (0.1 mg/kg, i.p.) attenuated the potentiation of startle produced by intra-amygdala infusions of pentagastrin. Finally, intra-amygdala infusion of the CCK B receptor-selective antagonist PD-135158 (10 g) blocked the potentiation of startle produced by i.c.v. infusions of pentagastrin, suggesting that i.c.v. infusions of pentagastrin potentiate startle responses via activation of amygdala CCK B receptors. These results show that amygdala CCK B receptor-mediated mechanisms are involved in the potentiation of acoustic startle responses.

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“…These results appear striking since CCK2 receptors activation (especially the CCK2a subtype) by CCK agonists has been shown to be involved in stress-related behaviors leading to anxiogenic-like responses in mice (Harro et al 1993;. In addition, most of the studies have shown that the blockade of CCK2 receptors by selective antagonists induces anxiolytic-like responses in rodents (Rataud et al 1991;Singh et al 1991;Derrien et al 1994; see also reviews in Harro et al 1993;Shlik et al 1997;Daugé and Léna 1998). Therefore, the lack of behavioral modifications observed with CCK2 receptor-deficient mice, could be related to unknown compensatory processes.…”

Section: Discussionmentioning

confidence: 94%

Behavioral Profile of CCK2 Receptor- deficient Mice

Dauge

Sebret

Beslot

et al. 2001

Neuropsychopharmacology

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The cholecystokinin (CCK) neuropeptide has been identified in the brain (Vanderhaeghen 1975;Dockray 1976), the most abundant form corresponding to the C-terminal sulfated octapeptide fragment (CCK8). This neuropeptide interacts with the same affinity with two receptor types, designated CCK1 (previously named CCK-A) and CCK2 (previously named CCK-B) receptors, which both belong to the G-coupled receptor superfamily (Wank et al. 1992;Lee et al. 1993). However, the distribution of these two receptors is quite different since the CCK1-type is abundant in peripheral organs and in few discrete brain regions (Moran et al. 1986;Hill et al. 1987). In contrast, the CCK2-type is the predominant receptor found in the central nervous system, especially in cortical and limbic structures (Gaudreau et al. 1983;Moran et al. 1986;Pélaprat et al. 1987). On the other hand, the gastrinic receptor localized on stomach parietal cells was shown to be identical to the brain CCK2 receptor (Wank et al. 1992).Pharmacological data using selective CCK agonists or antagonists have shown that CCK receptors play an important role in anxiety and stress-related behaviors, nociception and memory processes (reviews in: Harro et al. 1993;Crawley and Corwin 1994;Shlik et al. 1997 NO . 5 CCK2 KO Mice and Behavior 691 be the differences in recognition of two affinity states for the CCK2 receptor, designated 2a and 2b (Durieux et al. 1986; Harper et al. 1999a,b) which could correspond to different couplings to G proteins of a single receptor, resulting in different intracellular events (Pommier et al. 1999) and subsequently in distinct behavioral responses (Derrien et al. 1994;Léna et al. 1999).A now currently used approach for analyzing the physiological role of a receptor is to generate, by genetic manipulations, mice invalidated for this receptor (Kieffer 1999).The behavioral profile of CCK2 receptor-deficient mice generated by gene targeting (Nagata et al. 1996;Miyasaka et al. 1999) was carried out in this work. We demonstrate that their emotional responses are not significantly different from those elicited by wild-type animals. In contrast, a motor hyperactivity, a deficit in some attention and/or memory processes, and a neurological/muscular impairment occurred in genetically modified animals. All these modifications will be discussed in terms of possible direct consequences resulting from CCK2 receptor inactivation and/or from compensatory processes due to this receptor invalidation. METHODS SubjectsCD1 mice (Charles River, Saint-Aubin les Elbeuf, France) (three months old) and CCK2/gastrin receptor deficientmice (three months old) coming from the original background of 129sv/C57BL/6 mice (Nagata et al. 1996) were used. Breeding and genotype analysis of the latter have been done by Transgenic Alliance (L'Arbresle, France). Male and female mice were used. They were housed (groups of 4-5 mice per cage) in the laboratory at least a week before the experiments, in a temperature (22 Ϯ 1 Њ C) and humidity (50% Ϯ 5%) controlled environment and ha...

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‘Anxiolytic’ effect of CCK-antagonists on plus-maze behavior in mice

Cited by 70 publications

References 11 publications

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Activation of Amygdala Cholecystokinin_BReceptors Potentiates the Acoustic Startle Response in the Rat

Behavioral Profile of CCK2 Receptor- deficient Mice

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‘Anxiolytic’ effect of CCK-antagonists on plus-maze behavior in mice

Cited by 70 publications

References 11 publications

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Activation of Amygdala CholecystokininBReceptors Potentiates the Acoustic Startle Response in the Rat

Behavioral Profile of CCK2 Receptor- deficient Mice

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Product

Resources

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Activation of Amygdala Cholecystokinin_BReceptors Potentiates the Acoustic Startle Response in the Rat