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

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Abstract.

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 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. Conclusion: 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.

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Rowland, N.E., Lo, J. & Robertson, K. Acute anorectic effect of single and combined drugs in mice using a non-deprivation protocol. Psychopharmacology 157, 193–196 (2001). https://doi.org/10.1007/s002130100789

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  • DOI: https://doi.org/10.1007/s002130100789

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