The effects of haloperidol treatment on the distribution of NK1 receptor immunoreactive neurons in guinea-pig brain

Previous studies have observed increased tachykinin NK1 receptor immunoreactivity (NK1-IR) in the prefrontal cortex in subjects with schizophrenia. Since the subjects were medicated the possibility of a treatment effect could not be excluded. Thus, the present study was undertaken to determine the effect of chronic treatment with the antipsychotic drug, haloperidol, on the distribution of NK1-IR neurons in the guinea-pig brain. Guinea pigs were treated each day for 21 days with either haloperidol (1 mg/kg) or vehicle and the brains were then processed for immunohistochemistry using an NK1 receptor-specific polyclonal antibody. NK1-IR neurons and fibres were abundant in the forebrain cortex and caudate putamen and more sparsely distributed in a number of other brain regions. The relative density of NK1-IR neurons was significantly increased in the forebrain cortex, but not in the caudate putamen in guinea pigs treated with haloperidol. This study has shown that haloperidol causes region-specific changes to the density of NK1-IR neurons. Whether these changes are related to the therapeutic effects or to the side effects of haloperidol in individuals with schizophrenia, remains to be determined.