The impact of antipsychotic drugs on food intake and body weight and on leptin levels in blood and hypothalamic ob-r leptin receptor expression in wistar rats.
OBJECTIVE
The aim of our study was to investigate the impact of typical and atypical antipsychotic drugs on leptin concentration in blood and changes in the receptor expression in the hypothalamus of male Wistar rats.


METHODS
From the age of 13 to 18 weeks, three groups of 20 animals were fed an average dose of 3.5 + 0.03 mg/ kg body weight (BW) haloperidol; 30.6 + 0.22 mg/kg BW clozapine; or 14.9 + 0.13 mg/kg BW ziprasidone in ground food pellets containing 15% fat. Twenty control animals received no drugs. Blood samples were taken at week 14, 16, and 19. Locomotor activity and exploratory behavior were measured using the alcove test at weeks 15 and 17. The expression of the hypothalamic leptin receptor in rat brains was determined by using a Western blot.


RESULTS
Rats medicated with haloperidol and ziprasidone showed a significantly decreased percentage weight gain and food consumption. We observed no differences in the alcove test, but locomotor activity was significantly reduced in the haloperidol group. Except for rats in the clozapine and ziprasidone groups, after 2 weeks of drug application, we found no changes in the leptin blood concentrations among the four groups or animals within each group. Moreover, we did not find specific differences in hypothalamic leptin receptor expression among the groups.


CONCLUSIONS
We concluded that in male Wistar rats during this treatment period, the tested drugs did not act directly on the leptin regulatory system. We recommend further studies using long-term treatment of different rat strains.
LVR Klinikum Düsseldorf, Kliniken der Heinrich-Heine-Universität, Düsseldorf, Germany.
Martina
M
von Wilmsdorff
Marie-Luise
ML
Bouvier
Uwe
U
Henning
Andrea
A
Schmitt
Wolfgang
W
Gaebel
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D003024:Clozapine / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D007031:Hypothalamus / Q000737:chemistry* / Q000187:drug effects; D020738:Leptin / Q000097:blood*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D054411:Receptors, Leptin / Q000032:analysis*; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D020738:Leptin; D010879:Piperazines; D054411:Receptors, Leptin; D013844:Thiazoles; C092292:ziprasidone; D003024:Clozapine; D006220:Haloperidol