The modification of the ethanol withdrawal syndrome in rats by di-n-propylacetate.

Abstract

Di-n-propylacetate (DPA), a drug known to increase brain gamma-aminobutyric acid (GABA) levels and to inhibit GABA-transamine (GABA-T) activity, was administered during the ethanol withdrawal period to rats made physically dependent upon ethanol. Under all conditions tested, 400 mg DPA/kg injected i.p. significantly reduced the withdrawal hyperexcitable state induced by acoustic stimulation. The effect was seen as early as 30 min after the administration of DPA and lasted for at least 2 hrs. Readministration of the same dose of DPA 6.5 hrs after its initial injection again mitigated withdrawal symptoms. A 200 mg/kg dose of DPA was significantly effective for only 1 hr after its administration. Neither dose led to mortality or observable tranquilization. The results suggest that DPA may be a useful agent in the control of the hyperexcitable state induced by ethanol withdrawal and that the GABA system may be involved in this state.