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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-12-3
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pubmed:abstractText |
Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A1 and A2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A1 and A2A receptors appear to play important but differential roles in the modulation of the discriminative-stimulus effects of methamphetamine and cocaine.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-(2-carboxyethyl)phenethylamino)...,
http://linkedlifedata.com/resource/pubmed/chemical/8-cyclopentyl-1,3-dimethylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine A1 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine A1 Receptor Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine A2 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine A2 Receptor Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Central Nervous System Stimulants,
http://linkedlifedata.com/resource/pubmed/chemical/Cocaine,
http://linkedlifedata.com/resource/pubmed/chemical/MSX 3 compound,
http://linkedlifedata.com/resource/pubmed/chemical/Methamphetamine,
http://linkedlifedata.com/resource/pubmed/chemical/N(6)-cyclopentyladenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Phenethylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Adenosine A1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Adenosine A2A,
http://linkedlifedata.com/resource/pubmed/chemical/Theophylline,
http://linkedlifedata.com/resource/pubmed/chemical/Xanthines
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-3565
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
307
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
977-86
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:14557381-Adenosine,
pubmed-meshheading:14557381-Adenosine A1 Receptor Agonists,
pubmed-meshheading:14557381-Adenosine A1 Receptor Antagonists,
pubmed-meshheading:14557381-Adenosine A2 Receptor Agonists,
pubmed-meshheading:14557381-Adenosine A2 Receptor Antagonists,
pubmed-meshheading:14557381-Animals,
pubmed-meshheading:14557381-Central Nervous System Stimulants,
pubmed-meshheading:14557381-Cocaine,
pubmed-meshheading:14557381-Conditioning, Operant,
pubmed-meshheading:14557381-Discrimination (Psychology),
pubmed-meshheading:14557381-Discrimination Learning,
pubmed-meshheading:14557381-Dose-Response Relationship, Drug,
pubmed-meshheading:14557381-Generalization (Psychology),
pubmed-meshheading:14557381-Male,
pubmed-meshheading:14557381-Methamphetamine,
pubmed-meshheading:14557381-Phenethylamines,
pubmed-meshheading:14557381-Rats,
pubmed-meshheading:14557381-Rats, Sprague-Dawley,
pubmed-meshheading:14557381-Receptor, Adenosine A1,
pubmed-meshheading:14557381-Receptor, Adenosine A2A,
pubmed-meshheading:14557381-Theophylline,
pubmed-meshheading:14557381-Xanthines
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pubmed:year |
2003
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pubmed:articleTitle |
Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats.
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pubmed:affiliation |
Preclinical Pharmacology Section, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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