Adolescent rats exposed to ehanol during gestation exhibit altered c-fos activity in infralimbic cortex

FABIO M.C.; NIZHNIKOV ME; SPEAR, N.E.; PAUTASSI RM

Sapporo

Congreso; 2012 International Society for Biomedical Research on Alcoholism (ISBRA) World Congress; 2012

Science Council of Japan

Background: Epidemiological and pre-clinical data indicate that prenatal ethanol exposure is a risk factor for heightened alcohol use and abuse later in life. Several hypotheses have been provided for this permissive effect. One takes into account that fetuses perceive the chemosensory properties of ethanol resulting from maternal intoxication and can learn that these odor cues predict the appetitive, rewarding effect of the drug. This associative process would ultimately lead to heightened seeking and ethanol intake during adolescence or adulthood (Spear & Molina, 2005). The mechanisms underlying the permissive effect of gestational ethanol on later ethanol preference, however, remain poorly understood. The present study employed adolescent rats exposed to ethanol during pregnancy and analyzed spontaneous and ethanol-induced brain activation in several brain areas associated with processing of reward stimuli and with the acquisition, retrieval and extinction of associative learning. Methods: Pregnant Wistar rats were given intragastric administrations of ethanol (2.0 g/kg) or vehicle on gestational days 17-20. Previous studies indicate that this pattern of prenatal ethanol exposure reliably increases ethanol intake during adolescence, when tested through two-bottle choice tests. On postnatal day 37 (i.e., adolescence) the offspring were challenged with ethanol (2.5 or 0.0 g/kg) or remain untreated, and then were tested for motor activity and emission of ultrasonic vocalizations (data shown in Fabio et al., 2010). Ninety-minutes later the adolescent?s brains were preserved and stained for c-Fos protein expression in several areas of the mesocorticolimbic pathway related to the reward system, including infralimbic cortex and nucleus accumbens (core and shell). Results: Adolescent exposed to ethanol during pregnancy exhibited reduced overall neural activity in infralimbic cortex. c-Fos staining was similar across prenatal treatments in nucleus accumbens core and shell. Conclusions: Previous studies indicate that infralimbic cortex is involved in extinction of learned associations and inactivation of infralimbic cortex has resulted in persistence of previously reinforced appetitive or aversive behavior. The main result of the present paper (i.e., reduced neural activity in infralimbic cortex after gestational ethanol) suggests that moderate and brief prenatal ethanol exposure could result in extinction deficits during adolescence. Future studies should analyze the reliability of this finding as well as its potential association with predisposition for heightened ethanol intake. Acknowledgements: Grants PIP CONICET 2010-2012, PICT PRH3 and support from SUNY Research Foundation.