Acute anorectic effect of single and combined drugs in mice using a non-deprivation protocol

Rationale: 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 housi ng conditions, and examine the effects of a serotonergic agent dexfenfluram ine (DFEN), a dopaminergic agent phentermine (PHEN), and a selective norepi nephrine uptake inhibitor thionisoxetine (TNIX) alone and in combination. M ethods: 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. Dos e-inhibition curves were determined for DFEN, PHEN, and TNIX alone and for fixed ratio combinations of DFEN with either PHEN or TNIX. Results: Each dr ug produced a near linear dose-inhibition curve with the 50% inhibitory dos es (DI50) of 5.6, 3.2 and 12.2 mg/kg, respectively. By isobolographic analy sis, the effects of the drug combinations were strictly additive. Conclusio n: The procedure described is highly suitable for testing anorectic drugs i n mice and is adaptable to a variety of housing conditions and diets. The D FEN+ PHEN combination was additive, which contrasts with its reported supra -additive effect in rats.