Selective A2A, but not A1 adenosine antagonists enhance the anticataleptic action of trihexyphenidyl in rats

In rats made cataleptic with haloperidol (5.32 mumol/kg), the bar test was used to assess the possible synergism between the muscarinic antagonist trihexyphenidyl (THP) and selective adenosine A(1) and A(2A) receptor antagonists. Neither catalepsy intensity nor latency were affected by a subthreshold dose of THP (0.33 mumol/kg). The selective adenosine A(1) antagonist 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX) (5.15 mumol/kg) caused a small, but significant reduction of catalepsy intensity that remained unchanged when combined with THP. DPCPX had no effect on catalepsy latency, either alone or combined with THP. In contrast, an equimolar dose of the selective adenosine A(2A) antagonist 4-(2-[7-amino-2-(2-furyl)1,2,4-triazolo[2,3-a]-[1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) (5.15 mumol/kg) produced a significant reduction of catalepsy intensity and increased catalepsy latency. Both effects were potentiated when ZM 241385 was combined with THP. The synergism was more evident when rats were pretreated with a subthreshold dose of ZM 241385 (1.55 mumol/kg) that was unable to modify catalepsy parameters when applied alone, but produced a significant reduction in catalepsy intensity and an increase in catalepsy latency when administered with THP. Catalepsy was unaffected by a combination of equimolar, subthreshold doses of DPCPX (1.55 mumol/kg) and ZM 241385 (1.55 mumol/kg). These findings indicate that the anticataleptic effect of anticholinergics is enhanced only by the selective blockade of adenosine A(2A) receptors. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.