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

Naunyn Schmiedebergs Arch Pharmacol. 1996 Apr;353(5):545-51. doi: 10.1007/BF00169174.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Binding, Competitive
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology
  • Cocaine / administration & dosage
  • Cocaine / metabolism
  • Cocaine / toxicity*
  • Conditioning, Psychological / drug effects
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / metabolism
  • Dopamine Uptake Inhibitors / toxicity*
  • Electrodes, Implanted
  • Electroencephalography / drug effects
  • Injections, Intraperitoneal
  • Male
  • Microcomputers
  • Motor Activity / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D1 / drug effects*
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / metabolism

Substances

  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Cocaine