Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in nijmegen wistar rats

Abstract

The aim of the study was to investigate the biphasic locom otor response to ethanol in rats. Based on the recent finding that high responders to novelty (HR) and low responders to novelty (LR), selected from an outbred Nijmegen W istar rat population, show differences in ethanol intake and preference, it was ini tially investigated to what extent H R and L R differ in their locom otor response to ethanol, A dose-response curve (0.2-2.0 g/kg, IP) was established using stan dardized activity boxes. H R showed a significant increase at 0.5 g/kg, followed by a significant decrease at doses 1.0-2.0 g/kg; LR showed only a decrease at doses 1.0-2.0 g/kg. Secondly, it was investigated to what extent stress altered the ethanol-induced increase and decrease, respectively. For that purpose, the ethanol-induced locom otor effects (0.5 and 1.0 g/kg) were analyzed in habituated and noil-habituated (stressed) H R and LR; habituation consisted of a 15-min adaptation period to the activity cages. Stress significantly enhanced the excitatory effects in H R , but had no effect on the sedative effects in H R and LR. Finally, the locom otor effects of sub-chronic treatm ent (7 days) with an excitatory (0.5 g/kg) or sedative (LO g/kg) dose were analyzed in H R and LR. The excitatory effect of 0.5 g /k g disappeared throughout the treatm ent in H R , whereas the sedative effects of 1.0 g/kg remained the same in H R and LR. It is con cluded that the mechanism underlying the ethanolinduced m otor excitation differs completely from that underlying the ethanol-induced sedation. Given the known differences in the m ake-up of the brain and endocrine system between H R and LR, these animals are suggested to be good models for studying the m ech anisms underlying the biphasic locom otor response to ethanol in rats.

Individual differences in rat locomotor activity are diminished by nicotine through stimulation of central nicotinic acetylcholine receptors

“…Previous research has found that novelty-induced activity can serve as a predictive variable for a rat's sensitivity to the behavioral effects of abused drugs. This list of behaviors includes self-administration [14,15,29], drug discrimination [13], context conditioning [17], bar-press suppression [6], and locomotor activity [16,29]. Much of the research just cited reports a positive relation between reactivity to novelty and the subsequent behavioral effect of interest.…”

“…For instance, rats that are more activated by exposure to a novel environment (HR) more readily self-administer amphetamine and are more sensitive to the locomotor-stimulant effects of amphetamine [29]. Novelty-induced activity has been found to also predict such behavioral effects as activity induced by cocaine and caffeine [16], ethanol-induced activity and ethanol self-administration [14,15], amphetamine-conditioned hyperactivity to contextual stimuli [17], cueing effects of amphetamine [13] and amphetamine barpress suppressant effects [6].Another factor contributing to the interest in novelty-induced activity is the potential insight it may provide into the behavioral and neural substrates underlying individual differences in drug abuse vulnerability. This idea is based, in part, on the assumption that the predictive relation just described likely refl ects an overlap in the mechanism(s) responsible Published in Physiology & Behavior 72 (2001) Abstract: An increasing body of research has focused on isolating factors that predict or alter individual differences in the behavioral and neural processes mediating the effects of abused drugs.…”

“…For instance, rats that are more activated by exposure to a novel environment (HR) more readily self-administer amphetamine and are more sensitive to the locomotor-stimulant effects of amphetamine [29]. Novelty-induced activity has been found to also predict such behavioral effects as activity induced by cocaine and caffeine [16], ethanol-induced activity and ethanol self-administration [14,15], amphetamine-conditioned hyperactivity to contextual stimuli [17], cueing effects of amphetamine [13] and amphetamine barpress suppressant effects [6].…”

Motor Stimulant Effects of Ethanol Injected into the Substantia Nigra Pars Reticulata: Importance of Catalase-Mediated Metabolism and the Role of Acetaldehyde

“…The activating effects of systemic administration of ethanol have typically been shown in mice (Read et al, 1960;Frye and Breese, 1981;Crabbe et al, 1982;Masur et al, 1986;Aragon et al, 1992a;Phillips and Shen, 1996;Correa et al, 1999aCorrea et al, , 2000Correa et al, , 2001Correa et al, , 2004b. Although some studies have shown that selectively bred alcohol-preferring rats can show ethanol-induced increases in locomotion (Paivarinta and Korpi, 1993;Colombo et al, 1998;Rodd et al, 2004), in most previous studies, peripheral administration of ethanol to other strains of rats failed to stimulate locomotor activity, and generally has resulted in a suppression of motor activity (Frye and Breese, 1981;Masur et al, 1986;Waller et al, 1986;Spivak et al, 1987;Aragon et al, 1989;Gingras and Cools, 1996;Correa et al, 2003a). More recently, through the use of intraventricular administration of ethanol directly into the brain, it has been demonstrated that central administration of ethanol in rats can induce locomotor activation (Correa et al, 2003a, b) and also increased operant responding on a DRL30 schedule, which is a sign of behavioral stimulant effects (Arizzi et al, 2003).…”

A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect inCaenorhabditis elegans

“…The excitatory effects of ethanol have been phenotypically characterized in several different species, yet the molecular mechanism by which ethanol acts as an excitatory drug remains uncharacterized (Gingras and Cools 1996;Addicott et al 2007;Arias et al 2009;Beckstead and Phillips 2009;Kong et al 2010;Rose et al 2013). Using the model organism C. elegans, we developed a hypercontraction assay to study both the excitatory effects of ethanol and the tolerance that develops to these effects.…”