Effects of clozapine, olanzapine and haloperidol on the microstructure of ingestive behaviour in the rat.
BACKGROUND
Antipsychotic drugs, particularly the newer atypical compounds, have been associated with rapid weight gain in a clinical setting. However, there are few reported animal models producing reliable hyperphagia correlating with the human weight gain liability of these drugs.


OBJECTIVE
To compare the effects of the classic neuroleptic haloperidol with the atypical antipsychotics clozapine and olanzapine on the microstructure of ingestive behaviour in rats.


METHODS
Male hooded Lister rats drank a palatable high-calorie fat emulsion (10% Intralipid) during 30-min test sessions and microstructural analyses were made following administration of each drug over a range of doses.


RESULTS
Clozapine (0.3 mg/kg) and olanzapine (0.1, 0.3, 1 mg/kg) significantly increased intake, whilst haloperidol (0.05, 0.1, 0.2 mg/kg) significantly decreased drinking. No significant changes in the latency to the first lick were observed following any of the drugs tested. Median interlick intervals showed small, dose-related increases after clozapine (3.0 mg/kg), olanzapine (0.3, 1.0 mg/kg) and haloperidol (0.1, 0.2 mg/kg). Olanzapine (1.0 mg/kg) significantly elevated the number of clusters of licking (bouts of licking separated by pauses greater than 500 ms), whilst clozapine and haloperidol did not. Mean cluster size (licks per cluster) was not affected by clozapine or olanzapine, but haloperidol (0.025, 0.05, 0.1, 0.2 mg/kg) produced marked, significant decreases in cluster size.


CONCLUSIONS
Clozapine and olanzapine increased fat intake whereas haloperidol did not, and this resembles the greater weight gain liability of atypical antipsychotics in humans. A delay or reduction of the post-ingestive satiety signal combined with preserved palatability appears to be the mechanism responsible for fat hyperphagia in rats treated with clozapine and olanzapine. Conversely, haloperidol leaves satiety unaffected but reduces the palatability of the fat emulsion resulting in reduced intake.
Hartfield
Abegale W
AW
Laboratory of Experimental Psychology, University of Sussex, BN1 9QG, Brighton, UK.
Moore
Nicholas A
NA
Clifton
Peter G
PG
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D003024:Clozapine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects*; D004435:Eating / Q000187:drug effects / Q000523:psychology; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects* / Q000523:psychology; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009068:Movement / Q000187:drug effects; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D014059:Tongue / Q000187:drug effects / Q000502:physiology
D014150:Antipsychotic Agents; D005217:Fat Emulsions, Intravenous; D001569:Benzodiazepines; D010890:Pirenzepine; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine