The effects of beta-adrenoceptor antagonists on a rat model of neuroleptic-induced akathisia.
Neuroleptic-induced defecation in rats in a well-habituated environment has been proposed as a model of the subjective component of akathisia. In this study, we examined the effects of two lipophilic beta-adrenoceptor antagonists - the non-selective drug propranolol and the relatively beta1-selective metoprolol - and one non-selective hydrophilic drug nadolol in this model. Young male Wistar rats were randomly assigned to one of eight groups (n = 12 in each group) and treated with haloperidol or vehicle, with or without one of the beta-antagonists. Haloperidol-treated rats had higher bolus counts than vehicle-treated rats, and this increase was significantly reversed by the lipophilic but not the hydrophilic beta-antagonists. This finding is consistent with the reported anti-akathisia effects of these drugs in humans, suggesting that this effect is central in origin and achievable with relatively selective beta1-antagonism. The B-antagonist drugs significantly reduced the cataleptic effect of haloperidol and this effect warrants further examination.
Sachdev
P S
PS
School of Psychiatry, University of New South Wales, and Neuropsychiatric Institute, The Prince Henry Hospital, Sydney, Australia. p.sachdev@unsw.edu.au
Saharov
T
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D017109:Akathisia, Drug-Induced / Q000503:physiopathology*; D000818:Animals; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D002375:Catalepsy / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects / Q000502:physiology; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D006220:Haloperidol / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009248:Nadolol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D014150:Antipsychotic Agents; D009248:Nadolol; D011433:Propranolol; D008790:Metoprolol; D006220:Haloperidol