INHIBITORY AND EXCITATORY EFFECTS OF ADENOSINE ANTAGONISTS ON SPONTANEOUS LOCOMOTOR-ACTIVITY IN MICE

The behavioral effect of the adenosine antagonists CPT, PACPX, DPCPX a nd PD 115,199 on spontaneous locomotor activity was investigated in mi ce after parenteral administration. CPT, PACPX and PD 115,199 affected locomotor activity in a biphasic way. Doses in the nanomolar/kg range significantly reduced locomotion (PACPX greater than or equal to PD 1 15,199>>CPT). Higher doses were progressively less active until they b ecame ineffective or slightly stimulated locomotion. NECA, a mixed A(1 )/A(2) agonist and CCPA, a highly selective A(1) agonist, also induced a biphasic behavior, with low doses stimulating and high doses inhibi ting locomotion. The stimulant effect of 1 nmol/kg NECA was antagonize d by depressant doses of antagonists, whereas antagonists-induced hypo motility was potentiated by a depressant dose of NECA (20 nmol/kg). It is suggested that the blockade of A(1) receptors by antagonists is pr obably responsible for reducing locomotor activity, whereas the activa tion of A(2) receptors by agonists is likely responsible for reducing locomotion in mice.