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Repeated, intermittent exposure to psychostimulants or stressors results in long-lasting, progressive sensitization of the behavioral effects of a subsequent amphetamine (AMPH) challenge. Although behavioral sensitization has also been observed following a single drug pretreatment, the sensitizing potential of a single exposure to stress is not clear. Both drug- and stress-induced sensitization depend on an enhanced dopaminergic neurotransmission in the mesolimbic DA system. Apart from responding to rewards, this system is also involved in responding towards aversive social stimuli. Therefore, social stressors may be particularly effective in inducing cross-sensitization to stimulant drugs. We examined the time course of sensitization to the locomotor effects of the stimulant, AMPH, following a single social stressor: a social defeat. Wistar rats were exposed in a resident intruder paradigm to an unfamiliar dominant male conspecific (Wild-Type Groningen), resulting in defeat. The locomotor effects of a subsequent AMPH challenge (0.25 or 1.0 mg/kg) were evaluated 3, 14, and 21 days later by scoring horizontal movement in an open field. AMPH had significantly larger locomotor-activating effects in animals that had been defeated 3 days earlier compared to nondefeated controls. However, this sensitized response was no longer present 14 or 21 days after defeat. Therefore, we conclude that social defeat induces short-lasting cross-sensitization to the locomotor effects of AMPH in rats, but is not sufficient for long-term sensitization. The transient enhancement of responses to dopaminergic drugs may be indicative of a temporary role of dopamine in the cascade of physiological and behavioral changes following social defeat. (C) 2004 Elsevier Inc. All rights reserved