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: Liqun Yu, Michael A Schwarzschild, Jiang-Fan Chen
• Journal: Neuroscience letters (Neurosci Lett) Vol. 393 Issue 1 Pg. 31-5 (Jan 23 2006) ISSN: 0304-3940 [Print] Ireland
• PMID: 16236444 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A2 Receptor Antagonists
• Antiparkinson Agents
• Caffeine
• Levodopa
• Oxidopamine

Topics

• Adenosine A2 Receptor Antagonists
• Analysis of Variance
• Animals
• Antiparkinson Agents (administration & dosage)
• Behavior, Animal (drug effects)
• Caffeine (administration & dosage)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Levodopa (administration & dosage)
• Mice
• Mice, Inbred C57BL
• Oxidopamine
• Parkinson Disease, Secondary (chemically induced, drug therapy)
• Random Allocation
• Time Factors