Role of Calcineurin in Nicotine-mediated Locomotor Sensitization.
From: Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: Aug 2007
- ISSN: 1529-2401
- Volume: 27
- Issue: 32
- Pages: 8571-80
- Medium: Internet
- Language: English
- Citation (JAMA): Addy Nii A, Fornasiero Eugenio F, Stevens Tanya R, et al. Role of Calcineurin in Nicotine-mediated Locomotor Sensitization.. J. Neurosci. Aug 2007;27:8571-80
Abstract
Calcineurin is a serine/threonine phosphatase that contributes to the effects of nicotine on calcium signaling in cultured cortical neurons; however, the role of calcineurin in behavioral responses to nicotine in vivo has not been examined. We therefore determined whether calcineurin blockade could alter nicotine-mediated locomotor sensitization in Sprague Dawley rats using systemic or brain region-specific administration of the calcineurin inhibitors cyclosporine or FK506. Systemic cyclosporine administration decreased calcineurin activity in the brain, attenuated nicotine-mediated locomotor sensitization, and blocked the effects of nicotine on DARPP32 (dopamine- and cAMP-regulated phosphoprotein-32) activation in the striatum. Direct infusion of calcineurin inhibitors cyclosporine or FK506 into the ventral tegmental area (VTA) also attenuated nicotine-mediated locomotor sensitization, whereas infusion of rapamycin, which binds to FK-binding protein but does not inhibit calcineurin, did not affect sensitization. Together, the data suggest that activation of calcineurin, particularly in the VTA, is a novel signaling event important for nicotine-mediated behavior and intracellular signaling.
Mesh Headings (Keywords): Animals, Calcineurin, Cyclosporine, Male, Motor Activity, Nicotine, Rats, Rats, Sprague-Dawley, Ventral Tegmental Area
Check for Full Text / PubMed Unique Identifier (PMID): 17687035
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