M. El Yacoubi et al., SCH 58261 and ZM 241385 differentially prevent the motor effects of CGS 21680 in mice: evidence for a functional 'atypical' adenosine A(2A) receptor, EUR J PHARM, 401(1), 2000, pp. 63-77
The acute motor effects elicited by drugs acting upon adenosine A(2A) recep
tors, namely the highly selective agonist CGS 21680 or the antagonists SCH
58261 and ZM 241385, were investigated in mice. CGS 21680 dose-dependently
(0.1-2.5 mg/kg i.p.) decreased horizontal and vertical motor activities. Th
e depressant effect of CGS 21680 (0.5 mg/kg i.p.) was maintained in mice pr
etreated by the adenosine receptor antagonist 8-( p-sulfophenyl)-theophylli
ne (10-30 mg/kg i.p.), which poorly penetrates the blood-brain barrier, but
was completely lost in adenosine A(2A) receptor knockout mice. Thus, the a
denosine A(2A) receptor is critically involved in motor activity. SCH 58261
(1-10 mg/kg i.p.) increased locomotion and rearing with a quick onset, but
for a shorter period in mice habituated to the environment than in mice un
familiar to it. ZM 241385 (7.5-60 mg/kg i.p.) stimulated horizontal and ver
tical activities with a slow onset at the two highest tested doses, similar
ly in naive and in habituated mice. The increase in locomotion elicited by
ZM 241385 (15-30 mg/kg i.p. and 10-20 nM i.c.v.) was retained in mice treat
ed by CGS 21680 (0.5 mg/kg i.p.) but that elicited by SCH 58261 (1-3-10 mg/
kg i.p. and 10-20 nM i.c.v.) partially subsided. In conclusion, both 'stria
tal-like'/'SCH 58261-sensitive' adenosine A(2A) receptors and 'ZM 241385-se
nsitive'/'atypical' CGS 21680 binding sites may mediate CGS 21680-induced m
otor effects. Moreover, our results suggest that 'atypical' CGS 21680 bindi
ng sites could be adenosine A(2A) adreceptors with a peculiar pharmacologic
al profile. (C) 2000 Elsevier Science B.V. All rights reserved.