Characterization of the rapid-onset type of behavioral sensitization to amphetamine in mice: role of drug-environment conditioning.

A rapid-onset type of behavioral sensitization (ROBS) has been demonstrated in rats treated with a single 'priming' injection of amphetamine (AMP). In that species, however, this phenomenon was restricted to AMP-induced stereotyped behavior (SB), not occurring for the locomotor-stimulant effect (LSE) of AMP and not reflecting environment-specific sensitization. In the present study, the ROBS was characterized in the mouse. Mice received a single 'priming' intraperitoneal injection of 5.0 mg/kg AMP which was paired or not with environment. At different intervals (3, 4 or 5 h) subgroups were tested for AMP (1.5 or 5.0 mg/kg)-induced SB or AMP (1.5 mg/kg)-induced open-field LSE. Results showed that: (1) in the absence of drug-environment association, a priming injection of AMP increased the SB induced by a 1.5 mg/kg AMP challenge injection given 3 h (but not 4 or 5 h) later; (2) when the dose of AMP challenge injection was increased to 5.0 mg/kg, an enhancement of SB was verified at all the intervals tested (3, 4, and 5 h); (3) when animals were tested in an open field, the priming injection of AMP produced an increase in the LSE of a 1.5 mg/kg AMP challenge injection, given 4 h later; (4) drug-environment association increased both SB and locomotion after a saline challenge injection and potentiated the rapid-onset sensitization of both behaviors in AMP-challenged mice. Collectively, these results demonstrate that the ROBS phenomenon also occurs in mice, is extended to AMP-induced LSE, and is markedly potentiated by (but does not depend on) environmental conditioning.