Withdrawal from chronic amphetamine elevates baseline intracranial self-stimulation thresholds.

Intracranial self-stimulation was assessed before, within, and after a chronic amphetamine treatment regimen. Amphetamine was given twice daily 5 days per week for 6 weeks at dosages escalating from 1 to 10 mg/kg per injection. Lateral hypothalamic self-stimulation rate-frequency functions were taken 36 h after the last injection in each weekly series and weekly for 3 weeks following the last injection. Frequency thresholds increased and maximal response rates decreased progressively as a function of amphetamine withdrawal during treatment; each returned to near normal levels within 2 weeks of the last injection. When subsequently tested under amphetamine, animals previously receiving the 6-week amphetamine treatment regimen had self-stimulation thresholds and maximal response rates that did not differ significantly from those of saline-treated control animals. These data confirm that chronic amphetamine treatment results in a dependence syndrome characterized in part by a phasic depression in the brain mechanism mediating the reinforcing effects of lateral hypothalamic electrical stimulation.