A comparison of cocaine, GBR 12909, and phentermine self-administration by rhesus monkeys on a progressive-ratio schedule. 2001

D Stafford, and M G LeSage, and K C Rice, and J R Glowa
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.

The dopamine reuptake inhibitor GBR 12909 and the dopamine releaser phentermine may have potential for the treatment of cocaine abuse in humans. Pre-session treatment with either drug can decrease cocaine-maintained responding in rhesus monkeys while not affecting food-maintained responding. Both drugs are self-administered, but in some reports the patterns of responding they maintain differ from typical cocaine-reinforced responding. This study compared self-administration of cocaine (1--100 microg/kg/inj), GBR 12909 (3--100 microg/kg/inj), and phentermine (10--170 microg/kg/inj) in rhesus monkeys on a progressive-ratio schedule. Individual unit doses of each drug were available across several consecutive sessions. Cocaine self-administration was typical: the average number of ratios completed per session was a bitonic (increasing/decreasing) function of unit dose. Phentermine self-administration was variable across subjects (two of four monkeys self-administered reliably); one subject exhibited clear signs of behavioral toxicity. Self-administration of GBR 12909 was similarly variable across subjects. In the two subjects that self-administered GBR 12909 reliably, self-administration of small to mid-sized unit doses was enhanced following exposure to large unit doses. These data indicate that differences in self-administration of these drugs can be observed under progressive ratio procedures. Further, the data add to existing evidence suggesting that phentermine and GBR 12909 have at least moderate potential to be abused by humans.

UI MeSH Term Description Entries
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D008297 Male Males
D010645 Phentermine A central nervous system stimulant and sympathomimetic with actions and uses similar to those of DEXTROAMPHETAMINE. It has been used most frequently in the treatment of obesity. Adipex-P,Duromine,Ionamine,Phentermine Hydrochloride,Adipex P,AdipexP,Hydrochloride, Phentermine
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D012055 Reinforcement Schedule A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent. Reinforcement Schedules,Schedule, Reinforcement,Schedules, Reinforcement
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012646 Self Administration Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. Administration, Self,Administrations, Self,Self Administrations
D018663 Adrenergic Agents Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. Adrenergic,Adrenergic Agent,Adrenergic Drug,Adrenergic Neuron Agents,Adrenergic Release Inhibitors,Adrenergic Synthesis Inhibitors,Sympathetic Transmitter Releasers,Adrenergic Drugs,Adrenergic Effect,Adrenergic Effects,Adrenergic Neurohumor Depleters,Adrenergic Neuron Drugs,Adrenergics,Agent, Adrenergic,Agents, Adrenergic,Agents, Adrenergic Neuron,Depleters, Adrenergic Neurohumor,Drug, Adrenergic,Drugs, Adrenergic,Drugs, Adrenergic Neuron,Effect, Adrenergic,Effects, Adrenergic,Inhibitors, Adrenergic Release,Inhibitors, Adrenergic Synthesis,Neurohumor Depleters, Adrenergic,Neuron Agents, Adrenergic,Neuron Drugs, Adrenergic,Release Inhibitors, Adrenergic,Releasers, Sympathetic Transmitter,Synthesis Inhibitors, Adrenergic,Transmitter Releasers, Sympathetic

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