Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats.
Antipsychotic drugs have been used effectively for the treatment of schizophrenia symptoms, but they are often associated with metabolic side effects such as weight gain and endocrine disruptions. To investigate the possible mechanisms of antipsychotic-induced metabolic effects, we studied the impact of chronic administration of a typical antipsychotic drug (haloperidol) and an atypical antipsychotic (risperidone) to male rats on food intake, body weight, adiposity, and the circulating concentrations of hormones and metabolites that can influence energy homeostasis. Chronic (28days) haloperidol administration had no effect on food intake, weight gain or adiposity in male rats, whereas risperidone treatment resulted in a transient reduction in food intake and significantly reduced body weight gain compared to vehicle-treated control rats. Whereas neither antipsychotic had any effect on serum lipid profiles, glucose tolerance or the circulating concentrations of hormones controlled by the hypothalamo-pituitary-thyroid (free T4), -adrenal (corticosterone), -somatotropic (IGF-1), or -gonadotropic axes (testosterone), haloperidol increased circulating insulin levels and risperidone increased serum glucagon levels. This finding suggests that haloperidol or risperidone induce distinct metabolic effects. Since metabolic disorders such as obesity and type 2 diabetes mellitus represent serious health issues, understanding antipsychotic-induced endocrine and metabolic effects may ultimately allow better control of these side effects.
Lin
En-Ju D
EJ
Neuroscience Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia. d.lin@garvan.org.au
Lee
Nicola J
NJ
Slack
Katy
K
Karl
Tim
T
Duffy
Liesl
L
O'brien
Elizabeth
E
Matsumoto
Izuru
I
Dedova
Irina
I
Herzog
Herbert
H
Sainsbury
Amanda
A
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D001066:Appetite / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000517:prevention & control; D004703:Endocrine System / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D006946:Hyperinsulinism / Q000139:chemically induced*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D013045:Species Specificity; D013739:Testosterone / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D014150:Antipsychotic Agents; D007328:Insulin; D013739:Testosterone; D005934:Glucagon; D006220:Haloperidol; D018967:Risperidone; D003345:Corticosterone