title: The effect of active and passive intravenous cocaine administration on the extracellular signal-regulated kinase (ERK) activity in the rat brain.
abstract: According to a current hypothesis of learning processes, recent papers pointed out to an important role of the extracellular signal-regulated kinase (ERK), in drug addiction. We employed the Western blotting techniques to examine the ERK activity immediately after cocaine iv self-administration and in different drug-free withdrawal periods in rats. To distinguish motivational vs. pharmacological effects of the psychostimulant intake, a "yoked" procedure was used. Animals were decapitated after 14 daily cocaine self-administration sessions or on the 1st, 3rd or 10th extinction days. At each time point the activity of the ERK was assessed in several brain structures, including the prefrontal cortex, hippocampus, dorsal striatum and nucleus accumbens. Passive, repeated iv cocaine administration resulted in a 45% increase in ERK phosphorylation in the hippocampus while cocaine self-administration did not change brain ERK activity. On the 1st day of extinction, the activity of the ERK in the prefrontal cortex was decreased in rats with a history of cocaine chronic intake: by 66% for "active" cocaine group and by 35% for "yoked" cocaine group. On the 3rd day the reduction in the ERK activity (25-34%) was observed in the hippocampus for both cocaine-treated groups, and also in the nucleus accumbens for "yoked" cocaine group (40%). On the 10th day of extinction there was no significant alteration in ERK activity in any group of rats. Our findings suggest that cortical ERK is involved in cocaine seeking behavior in rats. They also indicate the time and regional adaptations in this enzyme activity after cocaine withdrawal.
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Miszkiel
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Detka
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Cholewa
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Frankowska
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Nowak
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Bogusława
authors.initials: B
authors.lastname: Budziszewska
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Przegaliński
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: mal.fil@if-pan.krakow.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000201:enzymology* / Q000523:psychology; D005108:Extinction, Psychological / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D017208:Rats, Wistar; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000201:enzymology* / Q000523:psychology
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine
keywords: Cocaine; Extinction training; Extracellular signal-regulated kinase; Self-administration yoked procedure