Cholecystokinin (CCK-8) modulates vesicular release of excitatory amino acids in rat hippocampal nerve endings

Breukel, A.I.M.; Silva, F.H. Lopes da; Ghijsen, W.E.J.M.

doi:10.1016/s0304-3940(97)00678-2

Cited by 28 publications

(20 citation statements)

References 28 publications

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“…The hippocampus is one of the areas where overexpression of CCK-2R contributes to the onset of anxiety (Wang et al, 2003). Activation of CCK-2R in the hippocampus causes excitation of pyramidal neurons by releasing excitatory amino acids (Breukel et al, 1997), an effect that is antagonized by benzodiazepines (Bradwejn & de Montigny, 1984). Interestingly, deletion of the CCK-2R gene produces specific adaptive disturbances (Noble & Roques, 2002) reminiscent of the exploratory pattern exhibited by HR rats.…”

Section: Discussionmentioning

confidence: 99%

The CCK-system underpins novelty-seeking behavior in the rat: Gene expression and pharmacological analyses

2008

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Cholecystokinin (CCK) and its receptor CCK-2R have been shown to promote emotional responsivity and behavioral sensitization to psychostimulants in the rat. An animal model has been developed based on locomotor response to a novel inescapable environment. Animals exhibiting consistent differences in locomotor response to novelty have been termed as High and Low Responder rats (HR and LR respectively). This paradigm is deemed to model sensation-seeking, a personality trait closely associated with substance abuse. The present study provides genetic and pharmacological evidence that the CCK-ergic system modulates this behavior. Distinctive patterns of CCK-related gene expression in HR and LR animals occurred beyond the mesolimbic pathways. CCK gene expression was higher in hippocampus, amygdala, and prefrontal cortex, but lower in the ventral tegmental area of HR relative to LR rats. Levels of CCK-2R mRNA were more elevated in LR animals in some areas of the forebrain such as the prefrontal cortex, nucleus accumbens, and hippocampus. Additionally, CCK-2R blockade with the antagonist LY225.910 (0.5 mg/Kg) removed phenotype differences in sustained exploration of novel stimuli (i.e., a novel-object) in HR and LR rats exposed to an enriched open-field test series. Finally, CCK-2R blockade also altered M 2 and 5-HT 7 receptor gene expression in the mediodorsal thalamus (a strategic structure for corticothalamic trafficking) in a phenotype-dependent manner. Taken together, the findings reported here suggest that distinct CCK-ergic function may contribute to promoting individual differences in noveltyseeking behavior.

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Section: Discussionmentioning

confidence: 99%

The CCK-system underpins novelty-seeking behavior in the rat: Gene expression and pharmacological analyses

2008

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“…In the light of their co-localization, it is not unlikely that following high-frequency stimulation conditions where both SV and LDCV exocytosis will take place, these transmitters could interact with each other either presynaptically and/or postsynaptically to control transsynaptic activity in time and space. Furthermore, independent paracrine signaling by secreted LDCV transmitters would supply the presynapse with an opportunity to spread its signal to neighbouring synapses or other cells [150]. In conclusion, continuation of research on differential signaling of presynaptic transmitter release will significantly broaden our insight in presynaptic contribution to versatility in neuronal communication.…”

Section: Differential Signaling In Presynaptic Neurotransmitter Releasementioning

confidence: 92%

Differential signaling in presynaptic neurotransmitter release

Ghijsen

Leenders

2005

CMLS, Cell. Mol. Life Sci.

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Neuronal communication is tightly regulated by presynaptic signaling, thereby temporarily and locally secreting one or more transmitters in order to exert propagation or modulation of network activity. In the last 2 decades our insight into the molecular regulation of presynaptic transmitter vesicle traffic and fusion has exponentionally grown due to the identification of specific functional interactions between presynaptic proteins involved in these processes. In addition, a plethora of extracellular and intracellular messengers regulate neurotransmitter release, occasionally leading to short- or long-term adaptations of the synapse to altered environmental signals. Important in this respect is the ability of various nerve terminals to diverge their output by differentiation in secretion of co-localized transmitters. This divergence in presynaptic signaling may converge in the postsynaptic target neuron or spread to neighbouring cells. In this review differential presynaptic signaling mechanisms will be related to their potential divergent roles in transmitter release.

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“…Cholecystokinin has been reported to increase GABA release in cerebral cortex (You et al 1997;Ferraro et al 1999;Siniscalchi et al 2003), neostriatum (You et al 1996), anterior nucleus accumbens (Lanza & Makovec, 2000) and hippocampus (Perez de la Mora et al 1993;Miller et al 1997). By contrast, CCK has also been reported not to change GABA release in the frontal-parietal cortex (Hickling et al 1997) and hippocampus (Migaud et al 1994;Breukel et al 1997). While the reasons underlying these controversies are unknown, CCK-mediated bidirectional modulation of GABA release may be relevant because most of those experiments were conducted by measuring the extracellular GABA concentration, which may reflect a neutralized effect of CCK on GABA release.…”

Section: Developmental Modulation and Physiological Significancementioning

confidence: 99%

“…Although CCK has been reported to increase GABA release from rat cortical slices (Ferraro et al 1999), rat nucleus accumbens (Lanza & Makovec, 2000) and the cerebral cortex of freely moving rats (Siniscalchi et al 2003), there are inconsistent results as to whether CCK modulates GABA release in the hippocampus (Perez de la Mora et al 1993;Migaud et al 1994;Breukel et al 1997;Miller et al 1997). Since most of the studies were conducted by measuring GABA concentration in the perfusate of either hippocampal slices or hippocampal synaptosomes, which may represent a neutralized effect of CCK in all regions of the hippocampal formation, we studied the effects of CCK on GABAergic synaptic transmission by recording GABA A receptor-mediated spontaneous IPSCs from different regions of the hippocampal formation to solve these controversies.…”

Section: Cck Bidirectionally Modulates Spontaneous Ipscsmentioning

confidence: 99%

“…Indeed, CCK has been reported to increase GABA release from hippocampal slices (Perez de la Mora et al 1993) and enhance GABA A receptor-mediated IPSCs in the CA1 region (Miller et al 1997), although two studies suggest that CCK does not change GABA release from rat hippocampal synaptosomes (Breukel et al 1997) and hippocampal slices (Migaud et al 1994). To solve these controversies and to determine the involved cellular and molecular mechanisms, we initially examined the effects of CCK on GABAergic synaptic transmission in the hippocampal formation.…”

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confidence: 99%

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Bidirectional modulation of GABAergic transmission by cholecystokinin in hippocampal dentate gyrus granule cells of juvenile rats

Deng

Lei

2006

The Journal of Physiology

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A receptor-mediated synaptic transmission in the hippocampal formation and then explored the underlying cellular mechanisms by focusing on the dentate gyrus region, where the highest levels of CCK-binding sites have been detected. Our results indicate that activation of CCK-B receptors initially and transiently increased spontaneous IPSC (sIPSC) frequency, followed by a persistent reduction. The effects of CCK were more evident in juvenile rats, suggesting that they are developmentally regulated. Cholecystokinin failed to modulate the miniature IPSCs recorded in the presence of TTX and the amplitude of the evoked IPSCs, but produced a transient increase followed by a reduction in action potential firing frequency recorded from GABAergic interneurons, suggesting that CCK acts by modulating the excitability of the interneurons to regulate GABA release. Cholecystokinin reduced the amplitude of the after-hyperpolarization of the action potentials, and application of paxilline or charybdotoxin considerably reduced CCK-mediated modulation of sIPSC frequency, suggesting that the effects of CCK are related to the inhibition of Ca 2+ -activated K + currents (I K(Ca) ). The effects of CCK were independent of the functions of phospholipase C, intracellular Ca 2+ release, protein kinase C or phospholipase A 2 , suggesting a direct coupling between the G proteins of CCK-B receptors and I K(Ca) . Our results provide a novel mechanism underlying CCK-mediated modulation of GABA release.

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Cholecystokinin (CCK-8) modulates vesicular release of excitatory amino acids in rat hippocampal nerve endings

Cited by 28 publications

References 28 publications

The CCK-system underpins novelty-seeking behavior in the rat: Gene expression and pharmacological analyses

The CCK-system underpins novelty-seeking behavior in the rat: Gene expression and pharmacological analyses

Differential signaling in presynaptic neurotransmitter release

Bidirectional modulation of GABAergic transmission by cholecystokinin in hippocampal dentate gyrus granule cells of juvenile rats

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