Techniques for assessing ethanol-mediated learning: first- and second order conditioned place preference, conditioned taste aversion, operant schedules and assessment of anxiety-like behaviors in animal models

PAUTASSI RM

San Pablo

Congreso; 2011 Meeting of the Latin-American Society for Biomedical Research on Alcoholism (LASBRA); 2011

Latin-American Society for Biomedical Research on Alcoholism (LASBRA)

Adult rats and adult mice differ in their sensitivity to ethanol´s effects when assessed through conditioned place preference (CPP) and ethanol-induced motor activation, common tests for ethanol’s motivational effects. Adult mice express robust CPP and behavioral activation when treated with ethanol. In contrast, adult rats avoid locations that signal the drug and usually fail to exhibit ethanol-induced motor activation. In terms of conditioned taste aversion (CTA) and ethanol-induced anxiolysis both species seem to be fairly and similarly sensitive to ethanol both effects. Recent data suggests that this typical species-related pattern of responsiveness to ethanol may be less obvious when testing takes place at adolescence. Adolescent mice exhibited CPP by ethanol when given a high ethanol dose (4 g/kg) but not with a more moderate dose (2.0 g⁄kg) and only after extensive training (Dickinson et al., 2008). Another study found that that adult mice expressed CPP by ethanol (2 g/kg); adolescent mice did so only after being exposed to substantial stress before conditioning (Song et al., 2007). Unlike mature mice, adolescent mice given repeated ethanol treatment did not show behavioral sensitization; instead, they exhibited gradually less ethanol-induced motor activity (Farias et al., 2009; also see Stevenson et al., 2008). On the other hand, Philpot et al. (2003) found CPP by ethanol in young (postnatal day 25, PD25, 0.2 g/kg) and late adolescent rats (PD45, 0.5 and 1 g/kg), whereas young adults (PD60) exhibited signs of conditioned aversion. We have recently found CPP by ethanol (1.0 g/kg) in preweanling (PD 13-14) and adolescent (PD 30-33) rats (Nizhnikov, Pautassi et al., 2009; unpublished data). Appetitive conditioning by ethanol at adolescence can also be obtained by a modified, second-order version of the CPP test (Pautassi et al. 2008; dose: 2.0 g/kg). Furthermore, adolescent rats exhibit ethanol-induced motor activation (Acevedo, Pautassi et al., in press). These activating effects were specific for high (2.5 g/kg) but not low (0.5 g/kg) ethanol dose, were similar across males and females, and emerged when testing occurred during the rising limb of the blood ethanol curve (5-11 min). There was a relationship between predisposition to these ethanol’s motor stimulating effects and ethanol affinity. Specifically, female rats selected for their high sensitivity to ethanol stimulation exhibited heightened ethanol intake when assessed in a three-bottle, forced access, intake test. Overall, these studies highlight the importance of assessing ethanol’s motivational effects across different developmental stages and species. Perhaps the apparent insensitivity of rats -- as compared with mice -- to ethanol’s rewarding effects changes when testing is shifted from adulthood to adolescence. This is, however, just a hypothesis. These species have not been yet tested in an equivalent mode during adolescence. The differences in sensitivity to ethanol’s hedonics may relate to differences in equipment, breeding protocols, or temporal or stimuli parameters across the studies.