Biomaterial Database

Pharmacological characterization of the discriminative-stimulus effects of GBR 12909. 1991

K F Melia, and R D Spealman

Harvard Medical School, New England Regional Primate Research Center, Southborough, Massachusetts.

Squirrel monkeys were trained to discriminate the selective dopamine uptake inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl)-methoxy] ethyl]-4-(3-phenylpropyl)piperazine) from saline in a two-lever drug-discrimination procedure. After i.v. injections of GBR 12909, 10 consecutive responses on one lever produced food, whereas after i.v. saline, 10 consecutive responses on the other lever produced food. By using a cumulative-dosing procedure, several inhibitors of monoamine uptake as well as dopamine receptor agonists and antagonists were evaluated for their ability to substitute for, or attenuate, the discriminative-stimulus effects of GBR 12909. Dopamine uptake inhibitors, including GBR 12909, cocaine, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane, mazindol, bupropion and methylphenidate, as well as the dopamine releasing drug (+)-amphetamine substituted fully (greater than 80% drug-lever responding) for the training dose of GBR 12909. In contrast, the selective norepinephrine uptake inhibitors, desipramine and talsupram, and the selective serotonin uptake inhibitor, citalopram, occasioned averages of only 13 to 19% drug-lever responding. The dopamine D1 agonist SKF 81297 (6-chloro-7,8-ddhydroxy-1-phenyl-2,3,4,5-tetrahydro-[1H]-3- benzazepine), the D2 agonists, (+)-4-propyl-9-hydroxynaphthoxazine and quinpirole, and the nonselective dopamine agonist, (-)-apomorphine, all occasioned a majority of responses (mean = 56-82%) on the drug-appropriate lever. The D1 partial agonists, R-SKF 38393 (R-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro- [1H]-3-benzazepine) and SKF 75670 (7,8-dihydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-[1H]-3-benzazepine), however, occasioned an average of no more than 21% drug-appropriate responding.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
D011954	Receptors, Dopamine	Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.	Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
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
D004193	Discrimination Learning	Learning that is manifested in the ability to respond differentially to various stimuli.	Discriminative Learning,Discrimination Learnings,Discriminative Learnings,Learning, Discrimination,Learning, Discriminative
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
D012453	Saimiri	A genus of the family CEBIDAE consisting of four species: S. boliviensis, S. orstedii (red-backed squirrel monkey), S. sciureus (common squirrel monkey), and S. ustus. They inhabit tropical rain forests in Central and South America. S. sciureus is used extensively in research studies.	Monkey, Squirrel,Squirrel Monkey,Monkeys, Squirrel,Saimirus,Squirrel Monkeys
D012457	Salicylamides	Amides of salicylic acid.
D014179	Neurotransmitter Uptake Inhibitors	Drugs that inhibit the transport of neurotransmitters into axon terminals or into storage vesicles within terminals. For many transmitters, uptake determines the time course of transmitter action so inhibiting uptake prolongs the activity of the transmitter. Blocking uptake may also deplete available transmitter stores. Many clinically important drugs are uptake inhibitors although the indirect reactions of the brain rather than the acute block of uptake itself is often responsible for the therapeutic effects.	Reuptake Inhibitors, Neurotransmitter,Transmitter Uptake Inhibitors, Neuronal,Inhibitors, Neurotransmitter Uptake,Uptake Inhibitors, Neurotransmitter,Inhibitors, Neurotransmitter Reuptake,Neurotransmitter Reuptake Inhibitors
D015259	Dopamine Agents	Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.	Dopamine Drugs,Dopamine Effect,Dopamine Effects,Dopaminergic Agents,Dopaminergic Drugs,Dopaminergic Effect,Dopaminergic Effects,Agents, Dopamine,Agents, Dopaminergic,Drugs, Dopamine,Drugs, Dopaminergic,Effect, Dopamine,Effect, Dopaminergic,Effects, Dopamine,Effects, Dopaminergic