Effect of depletion of brain 5-hydroxytryptamine by 5,7-dihydroxytryptamine on ethanol tolerance and dependence in the rat.
Brain 5-hydroxytryptamine (5-HT) was depleted in rats by intraventricular injection with 5,7-dihyroxytryptamine (5,7-DHT) prior to feeding rats a liquid diet containing ethanol. After withdrawal of ethanol, withdrawal reactions were significantly less severe in 5-HT-depleted rats than control rats. Sleeping times after a standard dose of ethanol or pentobarbitone were significantly prolonged in 5-HT-depleted rats. However, metabolic and pharmacodynamic tolerance developed to a similar extent in 5-HT-depleted rats as in control rats. It was concluded that 5-hydroxytryptaminergic neurons are not directly involved in the development of physical dependence on or tolerance to ethanol. Depletion of brain 5-HT by 5,7-DHT appears to result in a non-specific central nervous system depression that potentiates the depressant actions of ethanol and pentobarbitone and antagonises the hyperexcitability of ethanol withdrawal.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
D004102:Dihydroxytryptamines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D000431:Ethanol; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine