Differential effects of context on psychomotor sensitization to ethanol and cocaine

Abstract

Repeated drug injections lead to sensitization of their stimulant effects in mice, a phenomenon sometimes referred to as drug psychomotor sensitization. Previous studies showed that sensitization to cocaine is context dependent as its expression is reduced in an environment that was not paired with cocaine administration. In contrast, the effects of the test context on ethanol sensitization remain unclear. In the present study, female OF1 mice were repeatedly injected with 1.5 g/kg ethanol to test for both the effects of context novelty/familiarity and association on ethanol sensitization. A first group of mice was extensively pre-exposed to the test context before ethanol sensitization and ethanol injections were paired with the test context (familiar and paired group). A second group was not pre-exposed to the test context, but ethanol injections were paired with the test context (nonfamiliar and paired group). Finally, a third group of mice was not pre-exposed to the test context and ethanol was repeatedly injected in the home cage (unpaired group). Control groups were similarly exposed to the test context, but were injected with saline. In a second experiment, cocaine was used as a positive control. The same behavioral procedure was used, except that mice were injected with 10 mg/kg cocaine instead of ethanol. The results show a differential involvement of the test context in the sensitization to ethanol and cocaine. Cocaine sensitization is strongly context dependent and is not expressed in the unpaired group. In contrast, the expression of ethanol sensitization is independent of the context in which it was administered, but is strongly affected by the relative novelty/familiarity of the environment. Extensive pre-exposure to the test context prevented the expression of ethanol sensitization. One possible explanation is that expression of ethanol sensitization requires an arousing environment.

Transition from ethanol-induced sensitization to tolerance across early and late infancy in the rat

“…For instance, the way in which subjects from each age group respond to novelty seems to be involved in the ontogenetic transition from ethanol-induced sensitization to tolerance during infancy. Both the acute stimulation and the sensitized locomotor response induced by ethanol are highly dependent on novelty (Arias et al, 2009a;Didone et al, 2015;Hoshaw and Lewis, 2001;Meyer et al, 2005). Although we did not manipulate novelty in our study, other authors have reported that on PD 15 of the rat there is a peak in the locomotor response to a novel open-field (Campbell and Raskin, 1978), precisely the day on which we tested our subjects trained during the 2nd week, which could influence the expression of sensitization.…”

Resistance to ethanol sensitization is associated with a loss of synaptic plasticity in the hippocampus

“…Therefore, disturbances of synaptic plasticity properties in dorsal hippocampus CA1 may have direct impact on the NAc core activity and thus in locomotor or relapse processes linked to addiction. Because sensitization is a context‐dependent and or novelty/familiarity‐dependent phenomenon (Didone et al, ), it is possible that hippocampal plasticity may play an important role in this phenomenon and the fact LTD is lacking in resistant mice may thus explain, at least in part, the resistance to behavioral sensitization. LTD is known to be involved in novelty acquisition, including the learning context (Dong et al, ).…”

Long-term exposure to daily ethanol injections in DBA/2J and Swiss mice: Lessons for the interpretation of ethanol sensitization

“…Swiss mice were injected with 2.5 g/kg ethanol whereas DBA/2J mice were injected with 2.0 g/kg ethanol. These doses were selected as the optimal doses for inducing ethanol sensitization in these two strains of mice on the basis of previously published studies [4,9,10,18,20,21]. Pilot studies from our laboratory also confirmed slight differences between strains of mice in the proper ethanol doses to obtain a significant behavioral sensitization (unpublished data).…”

“…The same experimental protocol was used in all experiments to induce and test the behavioral sensitization to ethanol in the two strains of mice. The experimental protocol was adapted from previous ethanol sensitization studies from our laboratory [3,4,9]. On the first day of the experiment (P0, acclimation session), mice were acclimated to the apparatus and experimental procedure.…”

“…For example, it is unknown how ethanol sensitization evolves when ethanol exposure exceeds three weeks in mice. Indeed, the majority of ethanol sensitization studies used a period of ethanol exposure varying from 10 to 21 days [4,9–21]. In the 80’s, some early studies reported extensive periods of ethanol exposure, although they did not use standard sensitization protocol and did not document the daily development of ethanol sensitization.…”