THE NEGATIVE EFFECTS OF ALCOHOL HANGOVER ON HIGH-ANXIETY PHENOTYPE RATS ARE INFLUENCED BY THE GLUTAMATE RECEPTORS OF THE DORSAL MIDBRAIN

Author(s)

Ezequiel Leite, L. ^{[1, 2]} ; Nobre, M. J. ^{[3, 1, 2]}

Affiliation

^[1] Inst Neurociencias & Comportamento INeC, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Psicol, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Ribeirao Preto, SP - Brazil

^[3] Uni FACEF, Dept Psicol, BR-14401135 Franca, SP - Brazil

• Document type: Journal article
• Source: Neuroscience; v. 213, p. 93-105, JUN 28 2012.
• Web of Science Citations: 8

Abstract

Alcoholism is a chronic disorder characterized by the appearance of a withdrawal syndrome following the abrupt cessation of alcohol intake that includes symptoms of physical and emotional disturbances, anxiety being the most prevalent symptom. In humans, it was shown that anxiety may increase the probability of relapse. In laboratory animals, however, the use of anxiety to predict alcohol preference has remained difficult. Excitatory amino acids as glutamate have been implicated in alcohol hangover and may be responsible for the seizures and anxiety observed during withdrawal. The dorsal periaqueductal gray (DPAG) is a midbrain region critical for the modulation/expression of anxiety- and fear-related behaviors and the propagation of seizures induced by alcohol withdrawal, the glutamate neurotransmission being one of the most affected. The present study was designed to evaluate whether low- (LA) and high-anxiety rats (HA), tested during the alcohol hangover phase, in which anxiety is the most prevalent symptom, are more sensitive to the reinforcing effects of alcohol when tested in a voluntary alcohol drinking procedure. Additionally, we were interested in investigating the main effects of reducing the excitatory tonus of the dorsal midbrain, after the blockade of the ionotropic glutamate receptors into the DPAG, on the voluntary alcohol intake of HA and LA motivated rats that were made previously experienced with the free operant response of alcohol drinking. For this purpose, we used local infusions of the N-metil D-Aspartato (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate receptors antagonist DL-2-Amino-7-phosphonoheptanoic acid - DL-AP7 (10 nmol/0.2 mu l) and L-glutamic acid diethyl ester - GDEE (160 nmol/0.2 mu l) respectively. Alcohol intoxication was produced by 10 daily bolus intraperitonial (IP) injections of alcohol (2.0 g/kg). Peak-blood alcohol levels were determined by gas-chromatography analysis in order to assess blood-alcohol content. Unconditioned and conditioned anxiety-like behavior was assessed by the use of the fear-potentiated startle procedure (FPS). Data collected showed that anxiety and alcohol drinking in HA animals are positively correlated in animals that were made previously familiarized with the anxiolytic effects of alcohol. In addition, anxiety-like behavior induced during alcohol hangover seems to be an effect of changes in glutamatergic neurotransmission into DPAG possibly involving AMPA/kainate and NMDA receptors, among others. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 10/15157-4 - Trait anxiety and environmental enrichment as determining factors on the development and functioning of the reward and aversion circuitry in rats made dependent on alcohol or morphine
• Grantee: Manoel Jorge Nobre Do Espirito Santo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 08/05724-9 - Neurobiology of Drug Abuse: A behavioural and pharmacological study on fear and anxiety elicited in alcohol and morphine withdrawn rats, and the role of mesencephalic structures on the modulation of these responses.
• Grantee: Manoel Jorge Nobre Do Espirito Santo
• Support Opportunities: Regular Research Grants