Rats were administered 3, 6, and 12 mg/kg of d-amphetamine s.c. twice daily on a weekly increasing staircase schedule. On days 1, 7, 14, and 28 after the last injection of amphetamine the animals were challenged with 1 and 3 mg/kg of d-amphetamine and their behavior was observed. The 7-, 14-, and 28-day withdrawn animals required less amphetamine than controls to induce stereotyped behaviors. However, it was found that withdrawn animals and control animals were equally sensitive to the effects of apomorphine. Reserpine pretreatment eliminated the differences between control and withdrawn animals. alpha-Methyl tyrosine pretreatment blocked the effects of 1 but not 3 mg/kg of d-amphetamine in the withdrawn animals. Possible chemical mechanisms underlying the change in amphetamine sensitivity in the withdrawn animals are discussed.
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