Neuroleptic treatment for a substantial proportion of adult life: behavioural sequelae of 9 months haloperidol administration.

Rats were treated chronically with haloperidol (1.5 mg/kg per day in drinking water) for up to 9 months. At 1 week, 3.5 months and 9 months after commencing treatment, spontaneous activity in separate groups was depressed by 30-40%. Apomorphine stereotypy was also attenuated at 9 months. Following a 7-10 day withdrawal period after 9 months of treatment, both measures were elevated. Enhancement of spontaneous activity appeared to be at least in part characterised by a deficit in psychomotor habituation to the test apparatus. DA receptor blockade during haloperidol treatment for a substantial proportion of a rat's adult life was found to be an enduring effect, paralleling its antipsychotic action. Developing neurochemical supersensitivity was only manifested behaviourally after withdrawal of neuroleptic. The implications of such findings for the pathophysiology of schizophrenia and tardive dyskinesia and for the functional significance of dopamine receptor heterogeneity are discussed.