A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine.
BACKGROUND
Procedures for studying the effects of medications on satiation will assist the development of obesity medications.


OBJECTIVE
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.


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.


CONCLUSIONS
Drugs that enhance satiation for several types of food may be particularly effective for decreasing food intake.
Foltin
Richard W
RW
Division on Substance Abuse, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA. rwf2@columbia.edu
Danysz
Wojciech
W
Bisaga
Adam
A
D000818:Animals; D001067:Appetite Depressants; D003216:Conditioning, Operant / Q000187:drug effects; D020372:Dexfenfluramine / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005502:Food; D005518:Food Preferences / Q000187:drug effects / Q000523:psychology; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D010215:Papio; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule; D012201:Reward; D012527:Satiation / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012727:Sex Characteristics
D001067:Appetite Depressants; D020372:Dexfenfluramine; D018691:Excitatory Amino Acid Antagonists; D008559:Memantine; D016194:Receptors, N-Methyl-D-Aspartate; D017367:Selective Serotonin Reuptake Inhibitors