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 neuroactive steroid allopregnanolone is also a positive modulator of GABA-A receptors; therefore, we hypothesized that P and NP rats would respond differently to intraperitoneally administered allopregnanolone.


METHODS
Male P and NP rats were implanted with screw electrodes that overlay the frontal and parietal cortices and with a depth electrode aimed at the amygdala. Allopregnanolone (0.0-10.0 mg/kg ip) was administered 10 min before recording the EEG.


RESULTS
Allopregnanolone increased high-frequency power (8-32 Hz) in the cortex and amygdala of both P rats and NP rats. In addition, allopregnanolone 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 bandwidth, and increased EEG variability (16-50 Hz). The effects of allopregnanolone were qualitatively similar in P and NP rats. However, P rats were more sensitive to low doses of allopregnanolone in cortex, whereas NP rats responded to lower doses of allopregnanolone in the amygdala.


CONCLUSIONS
These data indicate that P and NP rats differ in their sensitivity to the EEG effects of allopregnanolone in the cortex and amygdala, which suggests that differences in GABAergic systems between P and NP rats may contribute to some of the differences observed in their behavioral repertoire.
Slawecki
C J
CJ
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA. cslawecki@scripps.edu
Purdy
R H
RH
Li
T K
TK
Walpole
T
T
Ehlers
C L
CL
D000428:Alcohol Drinking / Q000235:genetics* / Q000503:physiopathology; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats
D011280:Pregnanolone