Premium
Effects of Chronic Ethanol Consumption and Withdrawal on the Neuroactive Steroid 3α‐Hydroxy‐5α‐pregnan‐20‐one in Male and Female Rats
Author(s) -
Janis Gregory C.,
Devaud Leslie L.,
Mitsuyama Hiroki,
Morrow A. Leslie
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb05916.x
Subject(s) - corticosterone , endocrinology , medicine , endogeny , sensitization , ethanol , alcohol , estrous cycle , neuroactive steroid , receptor , chemistry , gabaa receptor , hormone , biochemistry , immunology
Prolonged alcohol (ethanol) consumption leads to the development of alcohol tolerance and cross‐tolerance to some benzodiazepines and barbiturates. In contrast, rats undergoing alcohol withdrawal are sensitized to the anticonvulsant effects of the endogenous GABAA receptor modulator, 3α‐hydroxy‐5α‐pregnan‐20‐one (3α, 5α‐THP). Alterations in endogenous, cerebral cortical levels of 3α, 5α‐THP during alcohol withdrawal could contribute to the observed sensitization to 3α, 5α‐THP. Therefore, this study investigated plasma and brain levels of 3α,5α‐THP, progesterone, and corticosterone during alcohol dependence and withdrawal in the rat. Plasma corticosterone, progesterone (a precursor of 3α,5α‐THP) and 3α,5α‐THP levels were unchanged in alcohol‐dependent animals. Cerebral cortical levels of 3α,5α‐THP decreased in dependent male animals, but not in dependent female rats. During alcohol withdrawal, plasma corticosterone and progesterone levels increased in male, but not female rats. However, neither plasma nor cerebral cortical 3α,5α‐THP levels were altered from control levels in male or female rats during alcohol withdrawal. Plasma and brain levels of 3α,5α‐THP were markedly higher in female compared with male rats. Cerebral cortical levels of 3α,5α‐THP during the diestrus phase of the estrus cycle were ˜4 to 6 ng/g, a concentration that may approach physiological relevance. These findings suggest that sensitization to 3α,5α‐THP during alcohol withdrawal is not mediated by elevations in brain levels of endogenous 3α,5α‐THP in male or female rats. However, elevations in circulating corticosterone and progesterone levels during ethanol withdrawal in male rats may underlie gender differences in allopreg‐nanolone sensitivity during ethanol withdrawal.