Sensitization to d-amphetamine after its repeated administration: evidence in EEG and behaviour.
After repeated administration of cocaine or d-amphetamine, a sensitization to their behavioural effects is frequently observed instead of a tolerance. In a previous study, it was shown that a moderate dose of d-amphetamine produced a pattern of EEG power spectrum which indicated a selective activation of D1-like dopamine receptors, whereas a larger dose induced a selective increase of power in the alpha-1 frequency band and, to a lesser degree, in the alpha-2 band, suggesting an additional activation of D2-like receptors. Furthermore, it was recently found that under a certain dosage and schedule, cocaine could produce a shift from a D1-characteristic to a D2-like EEG pattern. It was now studied, if the same is true for d-amphetamine. This drug was administered on 4 subsequent days (0.6 mg/kg i.p.); after an interval of 3 days, the same dose was administered. After repeated, but not a single administration, increases in the power of the alpha-1 and alpha-2 frequency bands were observed, suggesting a shift from activation of D1-like to additional activation of D2-like receptors. This shift was accompanied by a slight enhancement in stereotyped behaviour (sniffing). After a lower dose (0.2 mg/kg), no EEG effect could be observed, neither after a single nor after repeated administration.
Stahl
D
D
Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Germany.
Ferger
B
B
Kuschinsky
K
K
D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology
D000697:Central Nervous System Stimulants; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D003913:Dextroamphetamine