Extracellular signal-regulated mitogen-activated protein kinase inhibitors decrease amphetamine-induced behavior and neuropeptide gene expression in the striatum

• Published in: Neuroscience Vol. 138; no. 4; pp. 1289 - 1298
• Main Authors: Shi, X., McGinty, J.F.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2006; Elsevier
• Subjects: Aminoacetonitrile - analogs & derivatives; Aminoacetonitrile - pharmacology; Amphetamine - adverse effects; Amphetamine-Related Disorders - genetics; Amphetamine-Related Disorders - metabolism; Amphetamine-Related Disorders - physiopathology; Animals; Biological and medical sciences; Butadienes - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - physiopathology; Disease Models, Animal; Dynorphins - genetics; Enkephalins - genetics; Enzyme Inhibitors - pharmacology; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; in situ hybridization; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Medical sciences; Motor Activity - drug effects; Motor Activity - physiology; Neuropeptides - metabolism; Neuropharmacology; Nitriles - pharmacology; Pharmacology. Drug treatments; Phosphorylation - drug effects; preprodynorphin; preproenkephalin; Protein Precursors - genetics; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; psychostimulants; Rats; Rats, Sprague-Dawley; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Up-Regulation - drug effects; Up-Regulation - physiology; Vertebrates: nervous system and sense organs; psychostimulants; SDS; PPE; DMSO; PPD; PKA; TBST; CPu; ACSF; preproenkephalin; MAPK; AUC; NAc; MEK; CREB; preprodynorphin; DA; in situ hybridization; ERK; Molecular hybridization; CNS stimulant; Enzyme; Psychotropic; Central nervous system; Mitogen-activated protein kinase; Preproenkephalin; Basal ganglion; Corpus striatum; Gene expression; Extracellular; Neuropeptide; Encephalon; Amfetamine; Behavior
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2005.12.024

The aim of this study was to determine whether inhibition of the extracellular-regulated kinase signaling pathway decreases acute amphetamine-induced behavioral activity and neuropeptide gene expression in the rat striatum. Western blotting revealed that extracellular-regulated kinase1/2 phosphorylation was highly induced in the rat striatum 15 min after an acute amphetamine (2.5mg/kg, i.p.) injection without altering the total amount of extracellular-regulated kinase protein. In a separate experiment, the systemic injection of SL327, a selective inhibitor of extracellular regulated kinase kinase that crosses the blood–brain barrier, 1 h prior to amphetamine administration decreased amphetamine-induced vertical and horizontal activity. Quantitative in situ hybridization histochemistry showed that SL327 abolished the high levels of preproenkephalin and preprodynorphin mRNA induced by amphetamine in the striatum with no alteration of their basal levels. In another set of experiments, the hyperlocomotor activity induced by amphetamine was reduced by pretreatment with intra-striatal infusion of U0126. U0126 also blocked the amphetamine-induced increases in phospho-extracellular-regulated kinase and preproenkephalin and preprodynorphin gene expression in the striatum. These data indicate that activation of the extracellular-regulated kinase cascade contributes to the behavioral effects and changes in striatal neuropeptide gene expression induced by acute amphetamine.