There is increasing concern about the use and misuse of anorectic drugs, with more and more prescribed as adjuncts in weight control therapy. The present proposal will investigate the effects of these drugs on patterns of food intake in baboons maintained under minimal deprivation conditions. Food will be continuously available under an operant schedule that differentiates patterning of meals from pattern of pellet intake within meals. Schedule parameters will be chosen so that each animal will have control over initiation as well as termination of feeding throughout the day. Baseline patterns of food intake will be determined by measuring meal frequency, size, duration, and distribution of intake within each meal over several months. The effects of four manipulations on feeding will be assessed in order to compare those effects with later drug effects. Caloric prefeeding, acute deprivation cholecystokinin administration and the availability of an alternate energy source will all be parametrically manipulated. Complete dose-response functions for six amphetamine-like/stimulant anorectic drugs, three fenfluramine-like/sedative anorectic drugs and phenylpropanolamine will be determined. In addition, diazepam, known to increase food intake, and phencyclidine, which should decrease food intake by causing motor deficits, will also be tested. Profiles of the behavioral mechanisms of all these drugs when given on a single dose basis will be developed. Furthermore, the work will analyze the effects of long-term administration of low doses of d-amphetamine and fenfluramine on food intake; cross-tolerance to each other, phenylpropanolamine, and phencyclidine will be examined. The data collected in these studies will enhance the abuse liability data base of the anorectics and, in addition, provide important information about their behavioral mechanisms. This research will add to the large experimental data base on the self-administration of these compounds in primates, and provide important information for the analysis of the behavioral mechanisms of these drugs, e.g., effects on meal size and patterning. Such information will be useful both in evaluation of therapeutic efficacy and in understanding the basic processes involved in eating behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
7R01DA004130-07
Application #
3209319
Study Section
Special Emphasis Panel (SRCD (08))
Project Start
1986-05-01
Project End
1994-04-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Foltin, Richard W (2018) Self-administration of methamphetamine aerosol by male and female baboons. Pharmacol Biochem Behav 168:17-24
Foltin, Richard W; Evans, Suzette M (2018) Sex differences in the anorexigenic effects of dexfenfluramine and amphetamine in baboons. Exp Clin Psychopharmacol 26:335-340
Wu, Melody V; Shamy, Jul Lea; Bedi, Gillinder et al. (2014) Impact of social status and antidepressant treatment on neurogenesis in the baboon hippocampus. Neuropsychopharmacology 39:1861-71
Foltin, Richard W (2012) The behavioral pharmacology of anorexigenic drugs in nonhuman primates: 30 years of progress. Behav Pharmacol 23:461-77
Foltin, Richard W (2011) Consumption of palatable food decreases the anorectic effects of serotonergic, but not dopaminergic drugs in baboons. Physiol Behav 103:493-500
Foltin, Richard W; Danysz, Wojciech; Bisaga, Adam (2008) A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine. Psychopharmacology (Berl) 199:583-92
Bisaga, Adam; Danysz, Wojciech; Foltin, Richard W (2008) Antagonism of glutamatergic NMDA and mGluR5 receptors decreases consumption of food in baboon model of binge-eating disorder. Eur Neuropsychopharmacol 18:794-802
Foltin, Richard W; Haney, Margaret (2007) Effects of the cannabinoid antagonist SR141716 (rimonabant) and d-amphetamine on palatable food and food pellet intake in non-human primates. Pharmacol Biochem Behav 86:766-73
Zernig, Gerald; Ahmed, Serge H; Cardinal, Rudolf N et al. (2007) Explaining the escalation of drug use in substance dependence: models and appropriate animal laboratory tests. Pharmacology 80:65-119
Foltin, Richard W (2006) ""Tasting and wasting"" behavior in non-human primates: aberrant behavior or normal behavior in ""times of plenty"". Physiol Behav 89:587-97

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