Protection Against Acute MPTP‐Induced Dopamine Depletion in Mice by Adenosine A₁ Agonist

Abstract: The effects of the adenosine A₁ agonist N₆‐cyclohexyladenosine (CHA) on MPTP‐induced dopamine (DA) depletion in the striatum of C57BL/6 mice were studied. Twenty hours after a single injection of MPTP (30 mg/kg, s.c.), the toxin caused 62% depletion of striatal DA. CHA (0.2–3 mg/kg, s.c.), when given together with MPTP, prevented the toxin‐induced DA depletion in a dose‐dependent manner. This protective action was apparently mediated by the A¹ receptors, because this effect was selectively antagonized by pretreating the animals with the A₁ antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (25 mg/kg, i.p.) but not with the A₂ antagonist 1,3‐dipropyl‐7‐methylxanthine (25 mg/kg, i.p.). When CHA (3 mg/kg) was injected 5 h after MPTP administration, at which point striatal DA levels were already reduced significantly, a rapid and complete recovery of the striatal DA levels occurred. These neurochemical data suggest that the A₁ agonist CHA is potentially useful as a neuroprotective agent against MPTP‐induced toxicity.