Neonatal monosodium glutamate lesions alter neurosensitivity to ethanol in adult mice.
A number of studies have indicated a relationship between brain peptide activity and sensitivity to the behavioral effects of ethanol. Specifically, it has been suggested that ethanol effects are mediated by changes in the endogenous opioid peptides derived from the proopiomelanocortin (POMC) precursor. Most cell bodies containing brain POMC-derived peptides are found in the arcuate nucleus of the hypothalamus. Neonatal administration of monosodium glutamate (MSG) has been reported to destroy cell bodies of the arcuate nucleus. We treated WSC strain mice on postnatal Day 4 with a single SC injection of 4 mg/g MSG or saline. When adult, MSG and control mice were challenged with an IP injection of ethanol and its effect on body temperature, open field activity, or duration of loss of righting reflex was assessed. Blood ethanol concentration (BEC) was measured and the hypothalamic content of beta-endorphin like immunoreactivity (beta-EP) was determined by radioimmunoassay. beta-EP was markedly reduced in both females and males by MSG treatment. MSG-treated animals of both sexes showed significantly less ethanol-induced hypothermia than controls. BEC was higher in MSG-treated animals of both sexes than in controls, so the differences were not due to ethanol pharmacokinetics. beta-EP was generally lower in males. Duration of righting reflex was prolonged in MSG treated animals, and the reduction in open field activity was potentiated. These latter effects may be in part attributable to the higher BECs achieved in lesioned animals. These data suggest that beta-EP cell bodies in the arcuate nucleus of the hypothalamus mediate neurosensitivity to some effects of ethanol in mice, but further experiments will be necessary to implicate beta-EP specifically.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature / Q000187:drug effects; D004597:Electroshock; D004723:Endorphins / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D005971:Glutamates / Q000633:toxicity*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced*; D004856:Postural Balance / Q000187:drug effects; D011863:Radioimmunoassay; D012970:Sodium Glutamate / Q000633:toxicity*; D001615:beta-Endorphin
D004723:Endorphins; D005971:Glutamates; D000431:Ethanol; D001615:beta-Endorphin; D012970:Sodium Glutamate