Behavioural Brain Research 242 (2013) 191–199 Contents lists available at SciVerse ScienceDirect Behavioural Brain Research j ourna l ho mepage: www.elsevier.com/locate/bbr Research report Hippocampal-dependent Pavlovian conditioning in adult rats exposed to binge-like doses of ethanol as neonates Derick H. Lindquist ∗ The Ohio State University, Department of Psychology, 1835 Neil Avenue, Room 45, Columbus, OH 43210, United States h i g h l i g h t s ◮ Early ethanol exposure damages the brain, including the cerebellum and hippocampus. ◮ Hippocampal function assessed via trace eyeblink conditioning. ◮ Trace eyeblink conditioning was unimpaired by early ethanol exposure. ◮ Hippocampal function assessed via contextual gating of eyeblink conditioned response. ◮ Contextual control of conditioned response was unimpaired by early ethanol exposure. ◮ Results best explained by ethanol-induced cerebellar damage. a r t i c l e i n f o Article history: Received 10 September 2012 Received in revised form 12 December 2012 Accepted 13 December 2012 Available online 26 December 2012 Keywords: Pavlovian conditioning Eyeblink conditioning Cerebellum Hippocampus Fetal alcohol spectrum disorder (FASD) Fetal alcohol syndrome (FAS) a b s t r a c t Binge-like postnatal ethanol exposure produces significant damage throughout the brain in rats, including the cerebellum and hippocampus. In the current study, cue- and context-mediated Pavlovian condition- ing were assessed in adult rats exposed to moderately low (3E; 3 g/kg/day) or high (5E; 5 g/kg/day) doses of ethanol across postnatal days 4–9. Ethanol-exposed and control groups were presented with 8 ses- sions of trace eyeblink conditioning followed by another 8 sessions of delay eyeblink conditioning, with an altered context presented over the last two sessions. Both forms of conditioning rely on the brainstem and cerebellum, while the more difficult trace conditioning also requires the hippocampus. The hippocampus is also needed to gate or modulate expression of the eyeblink conditioned response (CR) based on con- textual cues. Results indicate that the ethanol-exposed rats were not significantly impaired in trace EBC relative to control subjects. In terms of CR topography, peak amplitude was significantly reduced by both doses of alcohol, whereas onset latency but not peak latency was significantly lengthened in the 5E rats across the latter half of delay EBC in the original training context. Neither dosage resulted in significant impairment in the contextual gating of the behavioral response, as revealed by similar decreases in CR production across all four treatment groups following introduction of the novel context. Results suggest ethanol-induced brainstem-cerebellar damage can account for the present results, independent of the putative disruption in hippocampal development and function proposed to occur following postnatal ethanol exposure. © 2013 Elsevier B.V. All rights reserved. 1. Introduction First defined four decades ago, fetal alcohol syndrome (FAS) rep- resents a pattern of growth retardation, facial dysmorphology, and cognitive impairment in infants born to women who drink while pregnant [1]. The teratogenic effects of alcohol are now recognized to result in a spectrum of physical and mental dysfunction, collec- tively termed fetal alcohol spectrum disorders (FASD) [2]. FASD is a recognized major public health problem [3], and one of the leading preventable causes of mental retardation [4]. The most severely ∗ Tel.: +1 614 292 2236; fax: +1 614 688 4733. E-mail address: lindquist.40@osu.edu afflicted children along the FASD continuum are diagnosed with FAS, which has a birth prevalence of 2–7 per 1000 births in the United States [4]. At the opposite end of the spectrum, alcohol- related neurodevelopmental disorder (ARND) refers to children that express the mental but not physical abnormalities associated with early alcohol exposure [5]. In fact, the estimated number of FASD children may be up to 10 times higher than reported due to difficulties in diagnosing ARND children in the absence of physical dysmorphology [6,7]. Across the five established FASD categories, afflicted children may exhibit pervasive deficits in learning, mem- ory, attention, and executive function [8–10]. A FASD animal model, in which rodents are treated with pre- and/or postnatal alcohol, has been successfully used over the last several decades to investigate the neurotoxic effects of alcohol 0166-4328/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.bbr.2012.12.030