Blockade of ERK Phosphorylation in the Nucleus Accumbens Inhibits the Expression of Cocaine-induced Behavioral Sensitization in Rats.

The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
Seungwoo KimJeong-Hoon Kim

Abstract

Repeated administration of psychostimulants such as cocaine leads to the development of behavioral sensitization. Extracellular signal-Regulated Kinase (ERK), an enzyme important for long-term neuronal plasticity, has been implicated in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site mediating the expression of behavioral sensitization by drugs of abuse, the precise role of ERK activation in this site has not been determined. In this study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single bilateral microinjections of PD98059 (0.5 or 2.0µ g/side), or U0126 (0.1 or 1.0µg/side), into this site dose-dependently inhibited the expression of cocaine-induced behavioral sensitization when measured at day 7 following 6 consecutive daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle or PD98059 alone produced no different locomotor activity compared to saline control. Further, microinjection of PD98059 (2.0µ g/side) in the NAcc specifically lowered cocaine-induced increase of ERK phosphorylation levels in this site, while unaffecting p-38 protein levels. These results indicate that ERK activation in the NAcc is necessary for the expression of cocaine-ind...Continue Reading

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Citations

Oct 20, 2012·BMC Pharmacology & Toxicology·Warren Winick-NgBettina E Kalisch
Nov 29, 2014·Addiction Biology·Bethania Mongi-BragatoLiliana M Cancela
Jul 6, 2013·Neurobiology of Learning and Memory·Milica CerovicRiccardo Brambilla
Dec 17, 2014·Frontiers in Pharmacology·Elena VashchinkinaEsa R Korpi
Sep 10, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Denisse ParedesDavid A Morilak

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Methods Mentioned

BETA
protein assay
electrophoresis
X-ray

Software Mentioned

Image Gauge

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