Intrastriatal injection of kainic acid prevents the development of postsynaptic dopamine receptor hypersensitivity after chronic haloperidol treatment.

Rats injected intrastriatally with kainic acid (KA), in contrast to sham-treated (control) animals, showed no tolerance toward catalepsy induced by chronic haloperidol treatment (28 days). After termination of chronic haloperidol treatment in control animals, apomorphine-induced stereotypy was significantly enhanced as compared to chronic saline-injected controls. Rats injected with kainic acid and treated with chronic haloperidol or saline showed no differences in apomorphine stereotypy. These results show that the development of tolerance and behavioural hypersensitivity after chronic neuroleptic treatment is mediated via striatal postsynaptic receptors sensitive to kainic acid lesions.