The study shows effects of the nonselective
adenosine A1/A2A receptor antagonist
caffeine and the selective A2A receptor antagonist
KW6002 on LPS-induced changes in the extracellular levels of
dopamine (DA),
glutamate,
adenosine,
hydroxyl radical, and A2A receptor density in the rat striatum. Intrastriatal LPS (10 μg) injection decreased extracellular level of DA and increased the level of
adenosine,
glutamate, and
hydroxyl radical on the ipsilateral side 24 h after LPS administration.
Caffeine (10 and 20 mg/kg i.p.) and
KW6002 (1.5 and 3 mg/kg i.p.) given once daily for 6 days and on the 7th day 2 h before and 4 h after LPS injection reversed the LPS-induced changes in extracellular levels of DA,
adenosine,
glutamate, and
hydroxyl radical production. Moreover, LPS-induced decrease in the striatal A2A receptor density was increased by
caffeine and
KW6002. In order to show the late LPS effect on oxidative damage of DA neurons, the contents of DA,
DOPAC, HVA, and
hydroxyl radical were determined 72 h after LPS (10 μg) administration into both striata. LPS decreased striatal and substantia nigra content of DA,
DOPAC, and HVA while increased striatal but not nigral content of
hydroxyl radical.
Caffeine (20 mg/kg) and KW60002 (3 mg/kg) given once daily for 6 days and on the 7th day 2 h before and 4 h after intrastriatal injection of LPS normalized the content of DA and its metabolites in both brain regions as well as decreased LPS-induced increase in the striatal level of
hydroxyl radical. In conclusion, our data demonstrated
antioxidant effects of
caffeine and
KW6002 in the inflammatory model of PD.