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.

Role of Dopamine Receptors on Electroencephalographic Changes Produced by Repetitive Apomorphine Treatments in Rats

“…These results are similar to changes induced by 0.6 mg/kg amphetamine (Stahl et al, 1997) and 20 mg/kg cocaine (Ferger et al, 1996). Lower doses of amphetamine or cocaine do not cause changes in either acute or chronic treatment (Ferger et al, 1996;Stahl et al, 1997), indicating that neural adaptation requires strong stimulation of dopamine receptors.…”

“…Haloperidol could also block acute apomorphine activity but not after chronic exposure, indicating a diminishing D2 receptor component. However, activation of D2 receptors after acute and/or repeated administration of (large doses of) psychostimulants leads to the activation of alpha1 band (7.0∼ 9.5 Hz) and alpha2 band (9.75∼12.5 Hz) that overlap with Alpha (8∼13 Hz) in this study (Kropf et al, 1989;Kropf and Kuschinsky, 1993;Ferger et al, 1994;Ferger and Kuschinsky, 1995;Ferger et al, 1996;Stahl et al, 1997). Delta1 and Delta2 band powers showed consistent increases unrelated to apomorphine treatment.…”

“…Some studies demonstrate good correlations between some EEG activity and stereotyped behavior during sensitization and conditioning with the psychostimulants amphetamine (Ferger et al, 1994;Stahl et al, 1997) and cocaine (Ferger et al, 1996), and the dopamine receptor agonist apomorphine (Kropf et al, 1989;1991). Electroencephalographic (EEG) spectral patterns and field potential are a sensitive tool for time-course studies of responses to different compounds acting on neurotransmitter systems (Ferger and Kuschinsky, 1995;Binienda et al, 2000).…”

“…The sensitization is particularly associated with dopaminergic systems (Vanderschuren and Kalivas, 2000;Steketee, 2003), which can be evaluated with EEG activity. For example, repeated administration of psychostimulants specifically increases the power of the alpha-1 and alpha-2 bands (Ferger et al, 1996;Stahl et al, 1997).…”

Topographic Imaging of Quantitative EEG in Response to Smoked Cocaine Self-Administration in Humans

“…Studies by Lukas et al (1988Lukas et al ( , 1990Lukas et al ( , 1995 have consistently reported an increase in alpha activity after cocaine, as well as other drugs of abuse, concurrent with episodic periods of euphoria. Similar to the clinical data, some animal studies have reported that acute cocaine and amphetamine treatment results in enhanced alpha activity, which was strongest in the alpha-1 bandwidth (7-9.5 Hz) and was blocked by D1 dopamine antagonists (Stahl et al, 1997;Ferger et al, 1994).…”