title: Cross-sensitization between caffeine- and L-dopa-induced behaviors in hemiparkinsonian mice.
abstract: Adenosine A(2A) receptor (A(2A)R) antagonists, including the non-specific adenosine antagonist caffeine, have been proposed as a novel, non-dopaminergic treatment strategy for Parkinson's disease (PD). However, the long-term interaction between caffeine and L-dopa treatment in PD models has not been characterized. We examined the interaction between caffeine and L-dopa following a repeated treatment paradigm in hemiparkinsonian mice. In contrast to the progressively sensitized rotational behavior induced by daily L-dopa (2.0 mg/kg) treatment, tolerance for the rotational response to daily caffeine (2.5 or 10 mg/kg) treatment tended to develop over several weeks. However, after a subsequent two-week washout, challenge with same drug demonstrated an extinction of the sensitized L-dopa-induced rotation, but a sensitization of the caffeine-induced rotation. In a cross-challenge paradigm, daily treatment of mice with L-dopa (compared to daily saline) produced a three-fold enhancement in the rotational response to a subsequent re-challenge with caffeine. Similarly, daily treatment of mice with caffeine produced a six-fold enhancement in the rotational response to a subsequent re-challenge with L-dopa. Furthermore, daily co-administration of caffeine plus L-dopa produced enhanced rotational behavior, compared to caffeine or L-dopa alone, indicating an additive or synergistic interaction between caffeine and L-dopa during repeated treatment. Cross-sensitization between caffeine and L-dopa following repeated treatment and their positive interaction during chronic co-adminstration in hemiparkinsonian mice suggest that repeated exposure to caffeine may alter L-dopa responses in PD.
authors.affiliation: Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, 02114, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Yu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schwarzschild
authors.forename: Jiang-Fan
authors.initials: JF
authors.lastname: Chen
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects*; D002110:Caffeine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007980:Levodopa / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D011897:Random Allocation; D013997:Time Factors
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D002110:Caffeine; D007980:Levodopa; D016627:Oxidopamine