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.