Harmine-, LON-954- and 5-hydroxytryptophan-induced tremors in rats withdrawn from ethanol.
The tremors induced by harmine, LON-954 (N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride) and 5-hydroxytryptophan (5-HTP) were studied in control rats and in rats withdrawn for 16-48 hrs from 6 to 9 days' ethanol administration. The frequencies and the intensities of the tremors were determined electronically. In control rats the frequency spectra of the tremors induced by harmine (20 mg/kg) and LON-954 (10 mg/kg) showed a narrow peak frequency at about 10 Hz. Atropine (1.2 mg/kg) altered neither the frequency nor the intensity of these tremors. 5-HTP (50 mg/kg) when given 3.5 hrs after iproniazid (100 mg/kg) induced tremor with peak frequencies at 6-7 Hz and 12 Hz. In ethanol-withdrawn rats treated with harmine or LON-954 the frequency analysis of tremor revealed a narrow peak frequency at about 12 Hz, which was neither the characteristic frequency of ethanol withdrawal tremor (6 Hz) nor that of harmine or LON-954 (10 Hz). The intensity of both harmine- and LON-954-induced tremor was significantly increased in ethanol-withdrawn rats. The ethanol-withdrawn rats were markedly sensitized to the effect of iproniazid+ 5-HTP, shown by deaths. The peak frequencies of this tremor were the same as those in control rats. The results suggest that harmine-induced tremor involves a dopaminergic-5-HT'ergic imbalance and the tremor induced by LON-954 a dopaminergic-cholinergic imbalance in the brain. The tremor in ethanol-withdrawn rats seems to be mediated by alterations in the activity of the cerebral 5-HT'ergic system.
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000431:Ethanol / Q000009:adverse effects*; D006247:Harmine / Q000494:pharmacology*; D008297:Male; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014202:Tremor / Q000139:chemically induced*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
D000470:Alkaloids; D000431:Ethanol; D006247:Harmine; C014908:LON 954; D014508:Urea; D010830:Physostigmine; D006916:5-Hydroxytryptophan