Spontaneous activity and apomorphine stereotypy during and after withdrawal from 3 1/2 months continuous administration of haloperidol: some methodological issues.

Rats were treated continuously with haloperidol (1.5 mg/kg/day in drinking water) for 3 1/2 months. Prior to withdrawal of neuroleptic both spontaneous activity and stereotypy responses to a low dose of apomorphine (0.15 mg/kg SC) were significantly reduced. Thus these indices of dopamine receptor blockade did not show tolerance or adaptation. When these measures were repeated shortly after haloperidol withdrawal stereotypy responses of the control group were indistinguishable from their responses on initial testing while haloperidol-withdrawn animals showed substantially more intense responsivity than on their initial assessment; the stereotypy responses of haloperidol-withdrawn animals were indistinguishable from parallel control values at 10--20 min after apomorphine challenge but were significantly above control values at 30--40 min after challenge. Control animals showed habituation of locomotor activity in the motility monitor when measures on the first and second assessments were compared while haloperidol animals showed indistinguishable activities on each assessment. Such methodological epiphenomena may influence the interpretation of studies on the functional sequelae of prolonged neuroleptic treatment and its subsequent withdrawal in the rat.