Ethanol-induced effects on opioid peptides in adult male Wistar rats are dependent on early environmental factors.
The vulnerability to develop alcoholism is dependent on both genetic and environmental factors. The neurobiological mechanisms underlying these factors are not fully understood but individual divergence in the endogenous opioid peptide system may contribute. We have previously reported that early-life experiences can affect endogenous opioids and also adult voluntary ethanol intake. In the present study, this line of research was continued and the effects of long-term voluntary ethanol drinking on the opioid system are described in animals reared in different environmental settings. Rat pups were subjected to 15 min (MS15) or 360 min (MS360) of daily maternal separation during postnatal days 1-21. At 10 weeks of age, male rats were exposed to voluntary ethanol drinking in a four-bottle paradigm with 5%, 10% and 20% ethanol solution in addition to water for 2 months. Age-matched controls received water during the same period. Immunoreactive (ir) Met-enkephalin-Arg6Phe7 (MEAP) and dynorphin B (DYNB) peptide levels were thereafter measured in the pituitary gland and several brain areas. In water-drinking animals, lower ir MEAP levels were observed in the MS360 rats in the hypothalamus, medial prefrontal cortex, striatum and the periaqueductal gray, whereas no differences were seen in ir DYNB levels. Long-term ethanol drinking induced lower ir MEAP levels in MS15 rats in the medial prefrontal cortex and the periaqueductal gray, whereas higher levels were detected in MS360 rats in the hypothalamus, striatum and the substantia nigra. Chronic voluntary drinking affected ir DYNB levels in the pituitary gland, hypothalamus and the substantia nigra, with minor differences between MS15 and MS360. In conclusion, manipulation of the early environment caused changes in the opioid system and a subsequent altered response to ethanol. The altered sensitivity of the opioid peptides to ethanol may contribute to the previously reported differences in ethanol intake between MS15 and MS360 rats.
Gustafsson
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Department of Pharmaceutical Biosciences, Division of Pharmacology, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
Zhou
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Nylander
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D000428:Alcohol Drinking / Q000523:psychology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D004777:Environment; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D008426:Maternal Deprivation; D018847:Opioid Peptides / Q000378:metabolism*; D011247:Pregnancy; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012306:Risk; D013315:Stress, Psychological / Q000378:metabolism
D002492:Central Nervous System Depressants; D004723:Endorphins; D018847:Opioid Peptides; D000431:Ethanol; D004744:Enkephalin, Methionine; D004399:Dynorphins; C036200:rimorphin