title: Increase in medial frontal cortex ERK activation following the induction of apomorphine sensitization.
abstract: Repeated high dose injections of the direct acting D1/D2 agonist apomorphine (APO) induces context specific behavioral sensitization. We assessed the effects of 2.0 mg/kg APO on open-field locomotor responses of rats over a 30 min period following either single or five daily APO injections. Acute injections increased locomotor activity, which was markedly increased in rats given 5 daily APO injections. This progressive increase in locomotion during the repeated APO treatments is indicative of behavioral sensitization. Immediately following the open-field test for the acute and the fifth apomorphine injection, the animals were euthanized and their brain tissue was prepared for immunohistochemistry. ERK immunoreactive nuclei in the medial prefrontal cortex (PFC), nucleus accumbens (NAcc), amygdala (AMYG) and lateral hypothalamus (LH) were quantified. The acute apomorphine injections increased ERK in all brain areas as compared to vehicle. Following the fifth apomorphine injection, ERK significantly increased in the PFC, decreased in the amygdala but was unchanged in the LH and NAcc. The selective increase in ERK activity in the PFC associated with behavioral sensitization, points to a possible pivotal role of the dopamine projection to the medial frontal cortex in the mediation of neural plasticity, considered to underlie the sensitization processes induced by dopaminergic drugs.
authors.affiliation: Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-600 RJ, Brazil.
authors.forename: Frederico Velasco Costa
authors.initials: FV
authors.lastname: Sanguedo
authors.affiliation: Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-600 RJ, Brazil.
authors.forename: Flávia Regina Cruz
authors.initials: FR
authors.lastname: Dias
authors.affiliation: Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Enrrico
authors.initials: E
authors.lastname: Bloise
authors.affiliation: Department of Biosciences, Federal University of São Paulo, Santos, SP, Brazil.
authors.forename: Isabel Cristina
authors.initials: IC
authors.lastname: Cespedes
authors.affiliation: Laboratory of Cellular and Tissue Biology, State University of North Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil.
authors.forename: Arthur
authors.initials: A
authors.lastname: Giraldi-Guimarães
authors.affiliation: Department of Entomology and Plant Pathology, State University of North Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil.
authors.forename: Richard Ian
authors.initials: RI
authors.lastname: Samuels
authors.affiliation: Research and Development (151), VA Medical Center, Syracuse, NY 13210, USA; SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Carey
authors.affiliation: Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-600 RJ, Brazil. Electronic address: marinete@uenf.br.
authors.forename: Marinete Pinheiro
authors.initials: MP
authors.lastname: Carrera
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D059333:Central Nervous System Sensitization / Q000187:drug effects; D018491:Dopamine Agonists / Q000008:administration & dosage; D004789:Enzyme Activation / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018491:Dopamine Agonists; D020929:Mitogen-Activated Protein Kinase Kinases; D001058:Apomorphine
keywords: Amygdala; Apomorphine; ERK; Medial prefrontal cortex; Nucleus accumbens; Sensitization