Acute anorectic effect of single and combined drugs in mice using a non-deprivation protocol.
BACKGROUND
Studies of the effect of anorectic drugs such as fenfluramine in mice have indicated the desirability of using experimental protocols that do not involve deprivation.


OBJECTIVE
We have developed a non-deprivation or "dessert" protocol for use in mice that are maintained in standard housing conditions, and examine the effects of a serotonergic agent dexfenfluramine (DFEN), a dopaminergic agent phentermine (PHEN), and a selective norepinephrine uptake inhibitor thionisoxetine (TNIX) alone and in combination.


METHODS
Female C57BL/6J mice were adapted to 30 min daily presentation of a gelatinized form of sweetened milk using a holder that hooks over the side of the cage during tests; food spillage and contamination are minimal. Dose-inhibition curves were determined for DFEN, PHEN, and TNIX alone and for fixed ratio combinations of DFEN with either PHEN or TNIX.


RESULTS
Each drug produced a near linear dose-inhibition curve with the 50% inhibitory doses (DI50) of 5.6, 3.2 and 12.2 mg/kg, respectively. By isobolographic analysis, the effects of the drug combinations were strictly additive.


CONCLUSIONS
The procedure described is highly suitable for testing anorectic drugs in mice and is adaptable to a variety of housing conditions and diets. The DFEN+ PHEN combination was additive, which contrasts with its reported supra-additive effect in rats.
Rowland
N E
NE
Department of Psychology, University of Florida, Gainesville 32611-2250, USA. nrowland@ufl.edu
Lo
J
J
Robertson
K
K
D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage*; D020372:Dexfenfluramine / Q000008:administration & dosage; D004338:Drug Combinations; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005508:Food Deprivation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010645:Phentermine / Q000008:administration & dosage; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage
D001067:Appetite Depressants; D004338:Drug Combinations; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; C093518:thionisoxetine; D010645:Phentermine; D020372:Dexfenfluramine