ADENOSINE A(2) RECEPTORS MODULATE HALOPERIDOL-INDUCED CATALEPSY IN RATS

The effect of adenosine A(1) and A(2) receptor agonists and antagonist s was investigated on haloperidol-induced catalepsy in rats. Pretreatm ent (i.p.) with the non-selective adenosine receptor antagonist, theop hylline, or the selective adenosine A(2) receptor antagonist, 3,7-dime thyl-1-propargylxanthine (DMPX), significantly reversed haloperidol-in duced catalepsy, whereas the selective adenosine A(1) receptor antagon ists, 8-phenyltheophylline and 8-cyclopentyl-1,3-dipropylxanthine prod uced no effect. Similar administration of the adenosine A(2) receptor agonists, 5'-(N-cyclopropyl)-carboxamidoadenosine and 5'-N-ethylcarbox amidoadenosine (NECA), and the mixed agonists with predominantly A(1) site of action, N-6-(2-phenylisopropyl) adenosine or 2-chloroadenosine , potentiated haloperidol-induced catalepsy. Higher doses of the adeno sine agonists produced catalepsy when given alone. However, N-6-cyclop entyladenosine, a highly selective adenosine A(1) receptor agonist, wa s ineffective in these respects. The per se cataleptic effect of adeno sine agonists was blocked by DMPX and the centrally acting anticholine rgic agent, scopolamine. Scopolamine also attenuated the potentiation of haloperidol-induced catalepsy by adenosine agonists. Further, i.c.v . administration of NECA and DMPX produced a similar effect as that pr oduced after their systemic administration. These findings demonstrate the differential influence of adenosine A(1) and A(2) receptors on ha loperidol-induced catalepsy and support the hypothesis that the functi onal interaction between adenosine and dopamine mechanisms might occur through adenosine A(2) receptors at the level of cholinergic neurons. The results suggest that adenosine A(2), but not A(1), receptor antag onists may be of potential use in the treatment of Parkinson's disease .