Effects of ritanserin on ethanol withdrawal-induced anxiety in rats

This study investigated the ability of ritanserin, a 5-HT2 antagonist, to m odify ethanol withdrawal (EW) symptoms in two animal models of anxiety: the elevated plus-maze (EPM) and the pentylenetetrazol (PTZ) discrimination as say. Long-Evans hooded rats were given a nutritionally balanced liquid diet containing 4.5% ethanol for 10 days. Twelve hours after removal of the eth anol diet, rats were tested in the EPM. A significant reduction in the open -aml activity and the number of total arm entries was observed, which is in dicative of EW. Acute ritanscrin (0.16-0.64 mg/kg, i.p., 60 min) had no eff ect on EW-induced anxiety-like behavior on the EPM. Ritanserin (0.08-0.64 m g/kg, i.p., b.i.d. 12 h) administered concurrently with the last 5 days of ethanol diet produced an increase in the time spent on the open arms of the EPM and reversed the EW-induced reduction in total arm entries. Rats train ed to discriminate between saline and PTZ (an anxiogenic drug), selected th e PTZ lever during EW. Chronic ritanserin (0.32 mg/kg, i.p., b.i.d.) did no t block PTZ lever responding during EW. On the rotorod, ritanscrin (0.32 mg /kg, i.p.) increased the motor incoordination induced by ethanol. In conclu sion, coadministration of ritanserin with ethanol prevented the development of EW-induced anxiety as measured by the EPM, but not in the PTZ drug disc rimination. (C) 2000 Elsevier Science Inc. All rights reserved.