Effects of ritanserin on ethanol withdrawal-induced anxiety in rats.
This study investigated the ability of ritanserin, a 5-HT2 antagonist, to modify ethanol withdrawal (EW) symptoms in two animal models of anxiety: the elevated plus-maze (EPM) and the pentylenetetrazol (PTZ) discrimination assay. Long-Evans hooded rats were given a nutritionally balanced liquid diet containing 4.5% ethanol for 10 days. Twelve hours after removal of the ethanol diet, rats were tested in the EPM. A significant reduction in the open-arm activity and the number of total arm entries was observed, which is indicative of EW. Acute ritanserin (0.16-0.64 mg/kg, i.p., 60 min) had no effect on EW-induced anxiety-like behavior on the EPM. Ritanserin (0.08-0.64 mg/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 trained to discriminate between saline and PTZ (an anxiogenic drug), selected the PTZ lever during EW. Chronic ritanserin (0.32 mg/kg, i.p., b.i.d. ) did not block PTZ lever responding during EW. On the rotorod, ritanserin (0.32 mg/kg, i.p.) increased the motor incoordination induced by ethanol. In conclusion, coadministration of ritanserin with ethanol prevented the development of EW-induced anxiety as measured by the EPM, but not in the PTZ drug discrimination.
Gatch
M B
MB
Department of Pharmacology, University of North Texas Health Science Center, Fort Worth 76107, USA. mgatch@hsc.unt.edu
Wallis
C J
CJ
Lal
H
H
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy*; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D004193:Discrimination Learning / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D016713:Ritanserin / Q000494:pharmacology / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D014151:Anti-Anxiety Agents; D002492:Central Nervous System Depressants; D016713:Ritanserin; D000431:Ethanol