The effects of
5,7-dihydroxytryptamine and
L-tryptophan treatment on
ethanol tolerance in the rat, as measured by the moving-belt test of motor impairment and by
hypothermia, were examined in separate studies. A 2 x 2 design was used for all experiments.
5,7-Dihydroxytryptamine (200 microgram in 20 microliter CSF) or vehicle alone was administered once into both lateral ventricles of the rat.
Desmethylimipramine was administered intraperitoneally prior to an
intraventricular injection of
5,7-dihydroxytryptamine to prevent the destruction of
norepinephrine.
L-Tryptophan (75 mg/kg p.o. twice daily) or water was administered chronically.
Ethanol (4--5 g/kg p.o.) or
sucrose was given daily, and the development of tolerance was monitored at 5--7-day intervals. Chronic
ethanol treatment produced tolerance to both the motor impairment and
hypothermia effects of
ethanol.
5,7-Dihydroxytryptamine and
L-tryptophan treatment did not alter either the motor impairment or
hypothermia produced by the initial dose of
ethanol.
5,7-Dihydroxytryptamine produced a 75% depletion of brain
5-HT and slowed the development of tolerance to
ethanol in both measurements. In contrast, elevation of
5-HT by
L-tryptophan (39% increase by a single dose) facilitated the development of tolerance to
ethanol, as seen in both measures. These findings support our hypothesis that brain
5-HT has a modulating role in the development of tolerance to
ethanol.