Differential effects of intermittent and continuous exposure to novel environmental stimuli on the development of amphetamine-induced behavioral sensitization in mice: Implications for addiction

Background: Previous studies have demonstrated a preventive effect of continuous environmental enrichment during early development on the vulnerability of rodents to drug addiction-related behaviors. Recently, it was demonstrated that a continuous environmental enrichment could eliminate already established addiction-related behaviors in mice. The present study compared the effects of intermittent or continuous exposure to novel stimuli during repeated amphetamine (Amp) treatment on the development of behavioral sensitization (an animal model of addiction-related neuroadaptations) in adult mice. Methods: Three-month-old male Swiss mice were treated with 2.5 mg/kg Amp every other day for 13 days in their home cages. Novel objects were presented in their home cages for 2 h on non-drug treatment days (experiment 1) or for 24 h/day during the 13 days of drug treatment (experiment 2). Seven days after the drug treatment had finished, the mice were challenged with 2.5 mg/kg Amp, and their locomotor activity was quantified in a familiar open field for 10 min. Results: Intermittent exposure to the novel objects did not modify the acute Amp locomotor stimulatory effect but potentiated the development of Amp-induced locomotor sensitization. This enhanced sensitization was due to increased locomotion in the central squares of the apparatus, which suggests anxiolysis or increased impulsiveness. Conversely, continuous exposure to the novel objects potentiated the acute Amp locomotor stimulatory effect and blunted the development of Amp-induced locomotor sensitization. Conclusions: We conclude that addiction-related behaviors can be differentially and critically modified depending on the schedule and period of the novelty exposure. (C) 2012 Elsevier Ireland Ltd. All rights reserved.