Handling history of rats modifies behavioural effects of drugs in the elevated plus-maze test of anxiety.

In rats naive to handling, but not in handling-habituated animals, baclofen (1 mg/kg) and (R,S) zacopride (1 microgram/kg) had significant anxiolytic effects, shown by an increased percentage of time spent on the open arms of the elevated plus-maze. The effects of buspirone were also modified by the animals' handling history and 200 micrograms/kg was significantly anxiogenic only in handling-habituated animals. The pattern of results is discussed in relation to biochemical differences already reported between handling-naive and handling-habituated animals, with particular respect to changes in the 5-HT system.