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The Journal of Neuroscience, October 1, 2001, 21(19):7474-7480

Cocaine- and Amphetamine-Regulated Transcript Peptide Modulation of Voltage-Gated Ca²⁺ Signaling in Hippocampal Neurons

Olena Yermolaieva¹, Jianguo Chen¹, Pastor R. Couceyro², and Toshinori Hoshi¹

¹ Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, and ² Department of Cellular and Molecular Pharmacology, Chicago Medical School, North Chicago, Illinois 60064

Administration of cocaine and amphetamine increases cocaine- and amphetamine-regulated transcript (CART) expression in the rat striatum (Douglass et al., 1995). CART mRNA is highly expressed in different parts of the human and rat brain, including hippocampus (Douglass et al., 1995; Couceyro et al., 1997; Kuhar and Yoho, 1999; Hurd and Fagergren, 2000). The presence of CART peptide 55-102 immunoreactivity in dense core vesicles of axon terminals suggests that the peptide may be released and may act as a neuromodulator (Smith et al., 1997) to induce neurophysiological and behavioral effects. Little is known, however, about CART peptide-responsive cells, receptor(s), or intracellular signaling mechanisms that mediate CART peptide action. Here we show that CART peptide 55-102 inhibits voltage-dependent intracellular Ca²⁺ signaling and attenuates cocaine enhancement of depolarization-induced Ca²⁺ influx in rat hippocampal neurons. The inhibitory effect of CART peptide 55-102 on Ca²⁺ signaling is likely mediated by an inhibition of L-type voltage-gated Ca²⁺ channel activity via a G-protein-dependent pathway. These results indicate that voltage-gated Ca²⁺ channels in hippocampal neurons are targets for CART peptide 55-102 and suggest that CART peptides may be important in physiology and behavior mediated by the hippocampus, such as certain forms of learning and memory.

Key words: hippocampus; neuropeptide; cocaine; CART; calcium; voltage-gated calcium channels

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21197474-07$05.00/0

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