L-type Ca2+ channels mediate adaptation of extracellular signal-regulated kinase 1/2 phosphorylation in the ventral tegmental area after chronic amphetamine treatment

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
A M RajadhyakshaB E Kosofsky

Abstract

L-type Ca2+ channels (LTCCs) play an important role in chronic psychostimulant-induced behaviors. However, the Ca2+ second messenger pathways activated by LTCCs after acute and recurrent psychostimulant administration that contribute to drug-induced molecular adaptations are poorly understood. Using a chronic amphetamine treatment paradigm in rats, we have examined the role of LTCCs in activating the mitogen-activated protein (MAP) kinase pathway in the ventral tegmental area (VTA), a primary target for the reinforcing properties of psychostimulants. Using immunoblot and immunohistochemical analyses, we find that in chronic saline-treated rats a challenge injection of amphetamine increases phosphorylation of MAP [extracellular signal-regulated kinase 1/2 (ERK1/2)] kinase in the VTA that is independent of LTCCs. However, in chronic amphetamine-treated rats there is no increase in amphetamine-mediated ERK1/2 phosphorylation unless LTCCs are blocked, in which case there is robust phosphorylation in VTA dopamine neurons. Examination of the expression of phosphatases reveals an increase in calcineurin [protein phosphatase 2B (PP2B)] and MAP kinase phosphatase-1 (MKP-1) in the VTA. Using in situ hybridization histochemistry and immun...Continue Reading

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Citations

Dec 22, 2007·Psychopharmacology·Herbert E CovingtonKlaus A Miczek
Sep 10, 2005·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Anjali M Rajadhyaksha, Barry E Kosofsky
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Dec 17, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Thomas P GiordanoAnjali M Rajadhyaksha
Sep 24, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kathryn SchierberlAnjali M Rajadhyaksha
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Dec 6, 2020·Signal Transduction and Targeted Therapy·Yehong DuZhifang Dong

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