Imipramine normalizes naturally-occurring and drug-induced differences in the exploratory activity of rats.

1 Exploratory activity of female hooded rats was measured in a Y maze on two occasions, 1 week apart. Locomotion (maze arm entries), rearing, and head-dipping into pots were scored for 5 min at each trial. 2 In control rats, differences between individuals in the amount of locomotion and rearing were consistent, as shown by significant test-retest correlations (r = +0.55, and +0.83 respectively). There was no correlation between head-dipping scores obtained in the two tests. 3 Imipramine (Imip) pretreatment before the second trial (10 mg/kg i.p on the 3 preceding days, and 2.5 mg/kg 1 h before) abolished these correlations. The scatter of the scores about the mean was also reduced by Imip, but there was no significant change in mean scores. Thus Imip appeared to have a 'normalizing' effect on locomotion and rears: after pretreatment, scores tended to be more uniform, and no longer reflected naturally-occurring individual differences. 4 Imip abolished the changes in exploratory activity produced by drugs which alter brain 5-hydroxytryptamine metabolism: p-chlorophenylalanine (100 mg/kg 24 h before testing) increased and DL-5-hydroxytryptophan (12.5 mg/kg 1 h before testing) decreased the fall in activity over the trial in saline-treated rats but not that in Imip-treated rats. In this case, Imip also produced an overall reduction in activity scores. 5 The normalizing effects of Imip on rat behaviour may be analogous to its therapeutic effects in human depressive disorders.