Harman induces preference for ethanol in rats: is the effect specific for ethanol?

Increasing concentrations of either ethanol, etonitazene, clomethiazole or midazolam were offered to male Wistar rats for 21 days. Between day 8 and day 21, the animals were treated with several doses of harman, harmalan, and tetrahydronorharman (tetrahydro-beta-carboline) by means of continuous intraventricular infusion. Harman and THN induced a significant preference for ethanol in a dose-dependent manner. Harman was approximately three times more potent than THN. The amount of ethanol consumed during the second and third weeks of the experimental period correlated with the harman concentration in the brain after the cessation of the treatment (p less than 0.01). Harman infusion attenuated the clomethiazole intake, whereas that of etonitazene and midazolam was not affected as compared with CSF-treated rats. By counting licking movements, it was found that the rats drank ethanol and water at distinct time periods with the pattern dependent on the concentration of the ethanol solution offered. The intervals between the maxima were 6 to 8 hours at low ethanol concentrations. Relatively high concentrations caused a disruption of the regular rhythms in favour of shorter ones with increasing intervals between the maxima (3 hr, 4 hr, 5 hr intervals). Harman treatment (27 nmol/hr) disturbed the regular rhythms at lower ethanol concentrations but mimicked the ultradian rhythm which was observed at high ethanol concentrations in CSF-treated animals. The observed coincidence of water and ethanol intake was uncoupled if the highest ethanol concentration in both treatments was offered. Thus, treatment with harman changed the rhythm of fluid intake in a direction which was detected in CSF-treated rats only at relatively high ethanol concentrations.