Year: 2007
Type: article
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.
Source: Journal of Neuroscience
Institutions: Yale University, Institut Interdisciplinaire de Neuroscience
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Awards: G1028864832, Role of the high affinity nicotine receptor in addiction, Tobacco Dependence & Risk Factors for Treatment Failure, Anatomical Basis for Nicotine Addiction, APA Diversity Program in Neuroscience, Role of Calcineurin in Nicotine Effects in Rats, Cognitive Dysfunction after Chronic Cocaine, G829525124, G9000233158, G9000341582, Anatomical Basis for Nicotine Addiction
OpenAlex ID: W2032524727