학술논문

A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine
Document Type
Original Paper
Source
Psychopharmacology. September 2008 199(4):583-592
Subject
Food intake
Baboon
Motivation
Satiation
Memantine
Dexfenfluramine
NMDA
Language
English
ISSN
0033-3158
1432-2072
Abstract
Rationale:Procedures for studying the effects of medications on satiation will assist the development of obesity medications.Objectives:Develop a procedure for measuring satiation during consumption of bland and highly palatable food and determine the effect of acute intramuscular administration of dexfenfluramine (DFEN), which increases serotonin levels, and memantine (MEM), which blocks N-methyl-d-aspartate receptors.Materials and methods:A modified progressive ratio (PR) procedure was used to track changes in reinforcing strength when a food was consumed. The response requirement increased after each reinforcement, and reinforcing strength was estimated using the breakpoint (BP), which was the last completed response cost. There was one preferred food (sweet candy) and one chow pellet PR session per week. During each session, four male and four female adult baboons experienced three 1-h PR trials, separated by 30 min. Chow pellets were available at all other times. We examined the BP for one to 20 candies or chow pellets. Drug effects were examined when baboons had access to one and ten candies or chow pellets.Results:BPs for candy were greater than for pellets. Varying the pellet/candy pieces per delivery produced an inverted U-shaped function on the first trial, i.e., maximal BP was observed for three items, and the BP for multiple items, but not a single item, decreased across trials, i.e., BP decreased with food intake and satiation. DFEN and MEM decreased responding with the greatest effects at ten deliveries, suggesting that DFEN and MEM enhanced satiation.Conclusion:Drugs that enhance satiation for several types of food may be particularly effective for decreasing food intake.