Effects of cocaine on the EEG power spectrum of rats are significantly altered after its repeated administration: do they reflect sensitization phenomena?

Abstract

It was previously shown that a moderate dose of cocaine (10 mg/kg i.p.) produces a pattern in the EEG power spectrum which indicates a preferential activation of dopamine D1-like receptors, namely a decrease of power in most of the frequency bands. In contrast, a large dose of cocaine (30 mg/kg i.p.) produces a decrease of power in most of the frequency bands as well, but a selective increase in the alpha-1 band, characteristic for an additional activation of dopamine D2-like receptors. In the present experiments, it was studied in rats, if in the course of sensitization, a shift from D1-like to additional D2-like receptor activation will occur or not. For this study, the animals were treated 10 times with cocaine (either 10 or 20 mg/kg) and, after a drug free interval of 4 days, tested with the same dose administered previously. Acute administration of 10 mg/kg of cocaine increased the locomotor activity slightly and its effect tended to be enhanced after repeated administration. Twenty mg/kg cocaine increased the locomotor activity more than the 10 mg/kg dose and its effect was significantly enhanced after repeated treatment. In addition, it was shown that the dose of 10 mg/kg of cocaine which activates D1- but not D2-like receptors is sufficient to elicit conditioned place preference. Ten mg/kg of cocaine produced a decrease of power in most of the frequency bands and this effect was slightly more pronounced after repeated treatment. Twenty mg/kg of cocaine acutely also produced a decrease in power in most of the frequency bands, but did not decrease the power in the alpha-1 band, being just at the threshold of activating D2-like receptors as well. Repeated administration led to a significant increase in power in the alpha-1 band and a less pronounced one in the alpha-2 band. This observation demonstrates that sensitization to cocaine can be manifest in the EEG and that after a certain dosage, a shift from an activation of D1-like dopamine receptors to an additional activation of D2-like receptors becomes obvious.

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).…”

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

“…produced an obvious shift in the EEG from a pattern characteristic for activation of D 1 -like receptors to one suggesting an additional activation of D 2 -like receptors (Ferger et al 1996).…”