Adenosine A1 and A2A receptor antagonists stimulate motor activity: evidence for an increased effectiveness in aged rats.
The motor effects of selective adenosine A1 and A2A receptor antagonists were tested in young (2 months) and aged (24 months) Wistar rats. In young rats, both the selective A2A receptor antagonist 5-amino-7-(2-phenylethyl)-2-2(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazo++ + lo[1,5-c]pyrimidine (SCH 58261, minimal effective dose 2 mg/kg intraperitoneally (i.p.)) and the selective A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT, minimal effective dose 1.2 mg/kg i.p.) stimulated motor activity. In old rats, both compounds induced significant motor activation starting from doses lower than those required in young animals. Specifically, the minimal effective doses of SCH 58261 and CPT in aged rats were 1 and 0.6 mg/kg i.p, respectively. The results indicate that both adenosine A1 and A2A receptors play a functional role in the control of motor activity, and, therefore, the blockade of both receptor subtypes is involved in the motor stimulating properties of methylxanthines. Also the evidence indicates, for the first time, that in aged animals the motor inhibitory adenosinergic tone seems to be increased with respect to young animals.
Popoli
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P
Department of Pharmacology, Istituto Superiore di Sanità, Rome, Italy.
Reggio
R
R
Pèzzola
A
A
Fuxe
K
K
Ferré
S
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; C053907:8-cyclopentyl-1,3-dimethylxanthine; D013806:Theophylline