Discriminative-stimulus effects of adenosine analogs: mediation by adenosine A2 receptors. 1988

R D Spealman, and V L Coffin
Harvard Medical School, New England Regional Primate Research Center, Southborough, Massachusetts.

Squirrel monkeys were trained to discriminate either the nonselective adenosine analog 5'-N-ethylcarboxamide adenosine (NECA) or the A1-selective analog N6-cyclopentyladenosine (CPA) from saline. After i.v. injections of 0.03 mumol/kg of NECA or 1.0 mumol/kg of CPA, 10 consecutive responses on one lever produced food, whereas after i.v. injections of saline, 10 consecutive responses on the alternate lever produced food. The discriminative-stimulus effects of the adenosine analogs NECA, CPA, 2-chloroadenosine and the R- and S-isomers of N6-phenylisopropyladenosine (PIA), of the adenosine antagonists caffeine and 8-cyclopentyltheophylline (CPT), and of selected drugs from other classes (haloperidol, pentobarbital, diazepam and morphine) were determined by administering cumulative doses i.v. before sequential components of the experimental session. All adenosine analogs engendered dose-related increases in the percentage of responses on the NECA- or CPA-associated levers reaching a maximum of greater than or equal to 90%. The rank order of potency was similar in both NECA-trained and CPA-trained monkeys: NECA greater than 2-chloroadenosine greater than or equal to CPA greater than or equal to R-PIA greater than S-PIA. None of the other drugs had discriminative-stimulus effects comparable to those of the adenosine analogs. In additional studies, the nonselective adenosine antagonist caffeine or the A1-selective antagonist CPT were administered before cumulative doses of NECA or CPA. Both adenosine antagonists blocked the discriminative-stimulus effects of NECA and CPA, with CPT being about one order of magnitude more potent than caffeine.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D010660 Phenylisopropyladenosine N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162. Isopropylphenyladenosine,L-Phenylisopropyladenosine,N(6)-Phenylisopropyl-Adenosine,L Phenylisopropyladenosine
D011983 Receptors, Purinergic Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP. Methyladenine Receptors,Purine Receptors,Purinergic Receptor,Purinergic Receptors,Purinoceptors,Purine Receptor,Purinoceptor,Receptors, Methyladenine,Receptors, Purine,Receptor, Purine,Receptor, Purinergic
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
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D000241 Adenosine A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Adenocard,Adenoscan
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
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D015762 2-Chloroadenosine 2-Chloroadenosine. A metabolically stable analog of adenosine which acts as an adenosine receptor agonist. The compound has a potent effect on the peripheral and central nervous system. 2 Chloroadenosine

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