Mianserin in the treatment of ethanol withdrawal in the rat: prevention of behaviors indicative of anxiety.

The present investigation was a pilot study to determine whether a single dose of mianserin, which produces long-term down-regulation of serotonin1C (5-HT1c) and 5-HT2 receptors, would prevent anxiogenic behaviors occurring during ethanol withdrawal as evaluated in the elevated plus maze. Male Long-Evans hooded rats were fed a liquid diet containing 4.5 percent ethanol for 4 days. Mianserin (20 mg/kg, i.p.) was injected on the morning of the third day of ethanol administration, or 48 hrs and 7 days prior to testing. When animals were tested either 12 hrs (acute withdrawal) or 5 days (protracted withdrawal) after the last dose of ethanol, anxiogenic behaviors were observed as a significant reduction in both percentage of open-arm entries and time spent on the open arms. In contrast, these anxiogenic behaviors were prevented by pre-injection with mianserin 48 hrs or 7 days prior to testing. Attenuation of this important symptom of ethanol withdrawal is of particular importance because, in addition to the nonaddicting properties of mianserin relative to current anxiolytics, the beneficial effects appear to be long lasting and can be achieved with a single dose.