Effects of allopregnanolone on the EEG of alcohol-preferring and alcohol-nonpreferring rats

Background: Alcohol preferring (P) and alcohol-nonpreferring (NP) rats have been shown to have differing behavioral and electrophysiological responses to drugs that are positive modulators of the gamma-aminobutyric acid type A (GABA-A) receptor complex, such as ethanol and benzodiazepines. The neuro active steroid allopregnanolone is also a positive modulator of GABA-A rece ptors; therefore, we hypothesized that P and NP rats would respond differen tly to intraperitoneally administered allopregnanolone. Methods: Male P and NP rats were implanted with screw electrodes that overl ay the frontal and parietal cortices and with a depth electrode aimed at th e amygdala. Allopregnanolone (0.0-10.0 mg/kg ip) was administered 10 min be fore recording the EEG. Results: Allopregnanolone increased high-frequency power (8-32 Hz) in the c ortex and amygdala of both P rats and NP rats. In addition, allopregnanolon e increased the predominant frequency of the cortical EEG in the 8 to 16 Hz bandwidth, decreased the predominant frequency in the 32 to 50 Hz bandwidt h, and increased EEG variability (16-50 Hz). The effects of allopregnanolon e were qualitatively similar in P and NP rats. However, P rats were more se nsitive to low doses of allopregnanolone in cortex, whereas NP rats respond ed to lower doses of allopregnanolone in the amygdala. Conclusions: These data indicate that P and NP rats differ in their sensiti vity to the EEG effects of allopregnanolone in the cortex and amygdala, whi ch suggests that differences in GABAergic systems between P and NP rats may contribute to some of the differences observed in their behavioral reperto ire.