Increase in medial frontal cortex ERK activation following the induction of apomorphine sensitization

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. (C) 2013 Published by Elsevier Inc.UENFFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)UENF-BrazilState Univ North Fluminense Darcy Ribeiro, Lab Anim Morphol & Pathol, Behav Pharmacol Grp, BR-28013600 Campos Dos Goytacazes, RJ, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Biosci, Santos, SP, BrazilState Univ North Fluminense Darcy Ribeiro, Lab Cellular & Tissue Biol, BR-28013600 Campos Dos Goytacazes, RJ, BrazilState Univ North Fluminense Darcy Ribeiro, Dept Entomol & Plant Pathol, BR-28013600 Campos Dos Goytacazes, RJ, BrazilVA Med Ctr, Syracuse, NY 13210 USASUNY Upstate Med Univ, Syracuse, NY 13210 USAUniversidade Federal de São Paulo, Dept Biosci, Santos, SP, BrazilWeb of Scienc

NMDA receptor blockade alters the intracellular distribution of neuronal nitric oxide synthase in the superficial layers of the rat superior colliculus

Nitric oxide (NO) is a molecular messenger involved in several events of synaptic plasticity in the central nervous system. Ca2+ influx through the N-methyl-D-aspartate receptor (NMDAR) triggers the synthesis of NO by activating the enzyme neuronal nitric oxide synthase (nNOS) in postsynaptic densities. Therefore, NMDAR and nNOS are part of the intricate scenario of postsynaptic densities. In the present study, we hypothesized that the intracellular distribution of nNOS in the neurons of superior colliculus (SC) superficial layers is an NMDAR activity-dependent process. We used osmotic minipumps to promote chronic blockade of the receptors with the pharmacological agent MK-801 in the SC of 7 adult rats. The effective blockade of NMDAR was assessed by changes in the protein level of the immediate early gene NGFI-A, which is a well-known NMDAR activity-dependent expressing transcription factor. Upon chronic infusion of MK-801, a decrease of 47% in the number of cells expressing NGFI-A was observed in the SC of treated animals. Additionally, the filled dendritic extent by the histochemical product of nicotinamide adenine di-nucleotide phosphate diaphorase was reduced by 45% when compared to the contralateral SC of the same animals and by 64% when compared to the SC of control animals. We conclude that the proper intracellular localization of nNOS in the retinorecipient layers of SC depends on NMDAR activation. These results are consistent with the view that the participation of NO in the physiological and plastic events of the central nervous system might be closely related to an NMDAR activity-dependent function