Time acts as a conditioned stimulus to control behavioral sensitization to amphetamine in rats

Repeated exposure to the psychostimulant drug, amphetamine, results in a persistent increase in the ability of the drug to elicit behavioral activation.(14,19) The development of sensitized responses to amphetamine involves long-lasting neuroadaptations within defined circuitry.(3,6,12,15,23) The behavioral expression of sensitization, however, can come under the control of specific environmental cues. Thus, the sensitized locomotor response to a challenge injection of amphetamine is greater if the drug is given in the environment previously associated with intermittent injections than if given in a different environmental context.(2,13,16,18,20,21) Contrary to the wealth of information on the significance of contextual cues, little is known about the importance of time cues in the expression of sensitized responding to amphetamine. In the present study we, therefore, asked whether time of injection might influence the expression of amphetamine sensitization. We found that time can readily act as a conditioned stimulus to control the expression of behavioral sensitization to amphetamine in rats. This finding is important for understanding the mechanisms underlying sensitization to psychostimulant drugs and its impact on behavior.