Sensitization to d-amphetamine after its repeated administration: evidence in EEG and behaviour

Abstract

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.