Role of NMDA glutamate receptors in the Dorsal Raphe Nucleus on the behavioural consequences of abstinence to ethanol

• Grant number: 12/01599-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2012
• End date: March 31, 2015
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Claudia Maria Padovan
• Grantee: Thiago Andre Viequetin
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Chronic consumption of ethanol (EtOH) and abstinence from it has been associated with disorders such as anxiety and depression. Several brain structures and neurotransmitter systems seem to be involved in mediating this effect. In animal models non-specific peripheric or intracerebral (Dorsal Raphe Nucleus) blockade of Nitric Oxide Synthetase (NOS) attenuates the anxiogenic effects induced by ethanol withdrawal. Nitric Oxide is synthesized from L-arginine (L-Arg) by the neuronal isoform of NOS in response to Ca+ influx induced by activation of N-methyl-D-aspartate (NMDA) glutamate receptors. Thus, the purpose of this study was to determine whether blockade of NMDA receptors can attenuate the anxiogenic effects induced by abstinence from chronic ethanol evaluated using the Elevated Plus Maze (EPM) Test. Male Wistar rats with guided cannulas aimed at the DRN will be submitted to acute (1 day) or chronic treatment (21 days) with 6% ethanol (v/v) followed by abrupt discontinuation of treatment for 48 h. After this period the animals will receive an intracerebral injection of AP-7 (NMDA receptor antagonist, dose to be determined) or saline (0,2µl) and five minutes later will be tested in the EPM. The number of entries and time spent in open and enclosed arms will be registered and analyzed by TWO-WAY ANOVA (p values will be set at 0.05).(AU)