Individual differences in amphetamine sensitization, behavior and central monoamines

Repeated amphetamine treatment results in behavioral sensitization in a high percentage of rats. Alterations to plasma corticosterone, neural monoamines and stress behavior can accompany amphetamine sensitization. Whether these changes occur following repeated amphetamine treatment in the absence of behavioral sensitization is not known. Male Sprague-Dawley rats were treated with amphetamine (2.5 mg/kg, i.p.) or saline once daily for 6 days. Amphetamine-induced locomotion and stereotypy, open-field anxiety behavior, plasma corticosterone and limbic monoamines were measured during withdrawal. Sixty-two percent of amphetamine-treated rats showed behavioral sensitization over the test periods. Only amphetamine-sensitized rats showed increased latency to enter the center of the open-field, as well as increased plasma corticosterone when compared to saline-treated controls. Amphetamine-sensitized rats showed increased dopamine concentrations in the shell of the nucleus accumbens and increased serotonin concentrations in the dorsal hippocampus, which were not observed in amphetamine-treated non-sensitized rats. These findings suggest that anxiety behavior, plasma corticosterone and limbic monoamines concentrations are altered by repeated amphetamine (2.5 mg/kg) treatment, and that these neuroendocrine and behavioral changes are often associated with sensitization to the psychostimulant effects of amphetamine.