We evaluated the effects of two anesthetics on the cocaine-induced electroencephalographic (EEG) desynchronization in male, Sprague-Dawley rats. One group was anesthetized with chloral hydrate (400 mg/kg, i.p., 80 mg/kg/h i.v. supplement; group A). The other group was anesthetized with pentobarbital sodium (50 mg/kg, i.p., 10 mg/kg/h i.v. supplement; group B). The degree of EEG desynchronization after cocaine administration (1.5 mg/kg, i.v.) was expressed as an increase in the mean power frequency (MPF) and a decrease in the root mean square (RMS). These maximal increases and decreases were observed to be larger in group A (MPF: 43.3 +/- 7.0% increase; RMS: 47.4 +/- 5.0% decrease) than in group B (MPF: 17.8 +/- 3.6% increase; RMS: 19.2 +/- 2.5% decrease). Our laboratory previously proved that dopaminergic neurotransmission at the medial prefrontal cortex (mPFC) participated in the cocaine-induced EEG desynchronization and that both D-1 and D-2 receptors were involved in the process. Therefore, in vivo microdialysis coupled with high performance liquid chromatography was used to quantify the changes of extracellular dopamine (DA) concentrations at the mPFC for 90 minutes at 10 minute intervals after 1.5 mg/kg cocaine i.v. injection. The extracellular DA increases in both groups was rapid and reached the maximal peak within 10 min. There was no significant difference in the maximal increase of DA between groups (group A: 375.2 +/- 35.77% versus group B: 332.2 +/- 16.69% over basal value). These results suggest that different anesthetics may differentially affect cocaine-induced EEG desynchronization and this difference has no bearing on the DA response in the mPFC.