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.
Wise
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RA
Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.
Munn
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D000661:Amphetamine / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000502:physiology*; D003913:Dextroamphetamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007026:Hypothalamic Area, Lateral / Q000502:physiology; D008297:Male; D051381:Rats; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D000661:Amphetamine; D003913:Dextroamphetamine