An animal model of nicotinic-acid-induced vasodilation: effect of haloperidol, caffeine and nicotine upon nicotinic acid response

Background: The normal vasodilatory response to ingestion of nicotinic acid (NA) is impaired in some patients with schizophrenia. It is unclear whethe r the impairment is a feature of the disorder itself or to a confounding fa ctor such as neuroleptics, caffeine or nicotine use. Methods: To address th is question in a controlled manner, we have developed an animal (rat) model of NA-induced vasodilation, in which response is monitored by measuring ch ange in skin temperature. Results: We observed that (i) acute administratio n of acetylsalicylic acid (100 mg/kg), caffeine (2.5 mg/kg) and haloperidol (0.1 or 0.5 mg/kg) and (ii) chronic administration of haloperidol (0.2 mg/ kg/day) significantly inhibited NA (30 mg/kg) response, whereas neither acu te (0.25 mg/kg) or chronic (0.5 mg/kg/day for 14 days) administration of ni cotine, or chronic administration of caffeine (5 mg/kg/day for 14 days) had any significant effect upon NA response. Conclusions: Our data suggest tha t at least one drug commonly used to treat schizophrenia (haloperidol) can interfere with the vasodilatory response to NA. Studies using nonmedicated patients with schizophrenia are required to determine whether reduced vasod ilatory response to NA in schizophrenia is a feature of the disorder or a c onsequence of treatment. (C) 2001 Elsevier Science B.V. All rights reserved .