Interstimulus interval determines whether ethanol produces conditioned place preference or aversion in mice

Abstract

DBA/2J mice were exposed to a distinctive floor stimulus (CS+) and ethanol (2 glkg) in a place conditioning paradigm. A different floor stimulus (CS-) was presented with saline. Mice injected just before or 30 min before CS exposure (Groups 0, -30) showed conditioned place preference, whereas mice injected right after exposure to the CS (Group 5) displayed place aversion (Experiment 1). None of the other groups (-120, -60, 15,60) showed place conditioning. Handling and saline injection given just before or after CS exposure were unable to produce place conditioning (Experiment 2). However, there was a positive relationship between ethanol concentration (10% vs. 20%) and test performance, suggesting that peritoneal irritation influences place conditioning (Experiment 3). Overall, these fmdings support the suggestion that intraperitoneal injection of ethanol produces an initial short-duration aversive effect that is followed by a longer lasting positive motivational effect.

FOS expression induced by an ethanol-paired conditioned stimulus

“…This dose has previously been shown to produce robust conditioned activation (Cunningham and Noble, 1992), place preference (e.g., Cunningham and Prather, 1992) and place aversion (e.g., Cunningham et al, 1997) in DBA/2J mice. Ethanol was administered IP in a volume of 12.5 ml/kg.…”

“…The procedure on CS-trials was similar, but each group was exposed to the hole floor (CS-) for 5 min and both injections were saline. Thus, Before-S mice were trained using a procedure known to produce CPP and After-S mice were trained using a procedure known to produce CPA (Cunningham et al, 1997). Delay-S mice were unpaired controls matched for ethanol experience, and Naïve-S mice were no-drug controls (Cunningham, 1993).…”

“…These two procedures were compared because previous research has shown that they produce opposite effects on behavior in a place-conditioning task. More specifically, pre-CS ethanol produces CPP whereas post-CS ethanol produces conditioned place aversion (CPA) (Cunningham and Henderson, 2000;Cunningham et al, 1997). Because these motivationally opposite behaviors are thought to be independently mediated (Cunningham et al, 2002), Before-S group mice were expected to have different patterns of FOS activation than After-S group mice, and both paired groups were expected to differ from unpaired-drug (Delay-S group) and drug-naive (Naïve-S group) control mice.…”

“…A differential conditioning procedure was used in which ethanol was paired with one stimulus (CS+) and saline with another stimulus (CS-). The basic parameters used for conditioning (i.e., dose, trial duration, number of trials) were selected on the basis of previous studies indicating their efficacy in producing conditioned changes in activity (Cunningham and Noble, 1992) and conditioned changes in preference/aversion for a paired stimulus (e.g., Cunningham et al, 1997). Although the response to CS-was not assessed during these experiments, CS-trials were included during the training phase in order to match the procedures in which we have previously demonstrated conditioned changes in activity and preference/aversion to the CS+.…”

Roles of the Nucleus Accumbens and Amygdala in the Acquisition and Expression of Ethanol-Conditioned Behavior in Mice

“…In previous experiments, this ethanol dose has reliably induced a strong CPP in DBA/2J mice (Cunningham et al, 2003) without detrimental behavioral effects of repeated injections at this dose or concentration (Cunningham et al, 1997). Saline was administered in a volume of 12.5 ml/kg.…”