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 whether the impairment is a feature of the disorder itself or to a confounding factor such as neuroleptics, caffeine or nicotine use.


METHODS
To address this question in a controlled manner, we have developed an animal (rat) model of NA-induced vasodilation, in which response is monitored by measuring change in skin temperature.


RESULTS
We observed that (i) acute administration of acetylsalicylic acid (100mg/kg), caffeine (2.5mg/kg) and haloperidol (0.1 or 0.5mg/kg) and (ii) chronic administration of haloperidol (0.2mg/kg/day) significantly inhibited NA (30 mg/kg) response, whereas neither acute (0.25mg/kg) or chronic (0.5mg/kg/day for 14 days) administration of nicotine, or chronic administration of caffeine (5mg/kg/day for 14 days) had any significant effect upon NA response.


CONCLUSIONS
Our data suggest that at least one drug commonly used to treat schizophrenia (haloperidol) can interfere with the vasodilatory response to NA. Studies using non-medicated patients with schizophrenia are required to determine whether reduced vasodilatory response to NA in schizophrenia is a feature of the disorder or a consequence of treatment.
Turenne
S D
SD
Cell Signaling Laboratory, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Ontario, M5T 1R8, Toronto, Canada.
Seeman
M
M
Ross
B M
BM
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000503:physiopathology; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009525:Niacin / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects*
D014150:Antipsychotic Agents; D009525:Niacin; D002110:Caffeine; D009538:Nicotine; D006220:Haloperidol