Sensitization to the effects of repeated amphetamine administration on intracranial self-stimulation: evidence for changes in reward processes.

The effects of daily administration of 1.0 mg/kg of D-amphetamine for 20 consecutive days on self-stimulation responding from the substantia nigra, and nucleus accumbens were evaluated at several current intensities. Raising current intensity increased rates of responding when electrodes were situated in these areas, and amphetamine significantly enhanced rates of responding from both brain regions. Moreover, the drug-induced response enhancements were facilitated further after repeated drug/test pairings. Although response sensitization was observed at several current intensities, it developed sooner at the lower current levels indicating that the sensitizing effect of repeated drug administration on self stimulation responding was not due to variations in locomotor activity or arousal levels induced by amphetamine treatment. Furthermore, sensitization was observed at current levels that engendered both high and low levels of responding, suggesting that the sensitization was unrelated to the rate dependent effects of the drug. Rather, it was argued that repeated amphetamine treatment sensitized animals to the rewarding properties of electrical brain stimulation. Possible neurochemical and behavioral mechanisms that may be involved in the development of reverse tolerance after repeated amphetamine treatment were discussed.