title: Effects of chronic caffeine on adenosine, dopamine and acetylcholine systems in mice.
abstract: Chronic ingestion of caffeine by male NIH Swiss strain mice leads in about 3 days to a significant increase in A1-adenosine, nicotinic and muscarinic receptors, and a significant decrease of beta 1-adrenoceptors in cerebral cortical membranes. Plasma levels of caffeine in the chronically treated mice range from 0.70 to 5.7 micrograms/ml. The changes in receptors reverse after withdrawal of caffeine within 7 days. An increase in nitrendipine binding sites, associated with L-type calcium channels, also occurs within 4 days and has reversed in 7 days after withdrawal. There is no change in the levels of striatal nicotinic receptors of D2-dopamine receptors, nor of [3H]cocaine binding to dopamine uptake sites. Levels of opioid receptors are either increased (delta) or unaltered (mu, kappa). sigma-Receptors are unaltered. Stimulations of striatal adenylate cyclase by forskolin, dopamine and NECA are not significantly affected after chronic caffeine ingestion. The adenosine agonist, NECA, reverses the amphetamine-elicited increases in locomotor activity and partly reverses the cocaine-elicited increases. The NECA dose-response curve is multiphasic (depression, stimulation and then depression) versus amphetamine in control mice, but only depressant versus amphetamine in chronic caffeine mice, while being multiphasic versus cocaine in both control and chronic caffeine mice. NECA reverses the stimulation of locomotor activity elicited by the muscarinic antagonist, scopolamine, and is more effective in the chronic caffeine mice. The behavioral depressant effects of the muscarinic agonist, oxotremorine, are not markedly altered after chronic caffeine ingestion.
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: D
authors.initials: D
authors.lastname: Shi
authors.forename: O
authors.initials: O
authors.lastname: Nikodijević
authors.forename: K A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: J W
authors.initials: JW
authors.lastname: Daly
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity; D009568:Nitrendipine / Q000378:metabolism; D011869:Radioligand Assay; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D018342:Receptors, Adrenergic, beta-1; D011950:Receptors, Cholinergic; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D011957:Receptors, Opioid; D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D002110:Caffeine; D009538:Nicotine; D009568:Nitrendipine; D000262:Adenylyl Cyclases; D000241:Adenosine; D000109:Acetylcholine