{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T22:05:28Z","timestamp":1771884328642,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,10,5]],"date-time":"2004-10-05T00:00:00Z","timestamp":1096934400000},"content-version":"vor","delay-in-days":4022,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[1993,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic caffeine ingestion (CCI) by male NIH Swiss strain mice results in a prolonged reduction in locomotor activity and alterations in response to caffeine, other xanthines, and adenosine analogs. Caffeine, the A<jats:sub>1<\/jats:sub> selective 8\u2010cyclopentyltheophylline (CPT), and the A<jats:sub>2<\/jats:sub>\u2010selective 3,7\u2010dimethyl\u20101\u2010propargylxanthine (DMPX) remain stimulatory and the bell\u2010shaped locomotor dose\u2010response curves are left\u2010shifted after CCI. The depressant effects of methylxanthines that are potent phosphodiesterase inhibitors remain after CCI. After CCI, mice became more sensitive to depressant effects of A<jats:sub>1<\/jats:sub>, mixed A<jats:sub>1<\/jats:sub>\/A<jats:sub>2<\/jats:sub>, and A<jats:sub>2<\/jats:sub> agonists. In the presence of caffeine the A<jats:sub>1<\/jats:sub>\u2010selective agonist N<jats:sup>6<\/jats:sup>\u2010cyclohexyladenosine (CHA), the mixed A<jats:sub>1<\/jats:sub>\/A<jats:sub>2<\/jats:sub> agonist 5\u2032\u2010N\u2010ethylcarboxamidoadenosine and the A<jats:sub>2<\/jats:sub>\u2010selective agonist 2\u2010[(2\u2010aminoethylamino)\u2010carbonylethylphenylethylamino]\u20105\u2032\u2010N\u2010ethylcarboxamidoadenosine (APEC) all have dose\u2010response curves, appearing to consist of initial depressant effects, then stimulatory effects, and finally pronounced depressant effects. The phasic character is reduced or absent after CCI. Synergistic depressant effects of combinations of CHA and APEC also appear reduced after CCI. \u00a9 1993 wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ddr.430300209","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T05:29:17Z","timestamp":1104557357000},"page":"104-110","source":"Crossref","is-referenced-by-count":14,"title":["Effects of combinations of methylxanthines and adenosine analogs on locomotor activity in control and chronic caffeine\u2010treated mice"],"prefix":"10.1002","volume":"30","author":[{"given":"Olga","family":"Nikodijevi\u0107","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth A.","family":"Jacobson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John 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