Behavioral interaction of adenosine and methylxanthines on central purinergic systems

Mice implanted with chronic indwelling cannulae were injected in the lateral cerebral ventricle with adenosine (ADO); an adenosine analogue, 5'-N-ethylcarboxamidoadenosine (NECA); a potent adenosine uptake inhibitor, papaverine (PAP); and a methylxanthine, 3-isobutyl-1-methylxanthine (IBMX). All drugs produced dose-related decreases in spontaneous locomotor activity and the order of potency for locomotor depression was: NECA much greater than IBMX greater than ADO, PAP. Further, the behavioral interaction of i.p. injections of caffeine with drug-induced locomotor depression was examined at a dose of caffeine which had no effect on locomotor activity when given alone. Caffeine antagonized the depressant effects of NECA at all doses. However, doses of IBMX producing only behavioral depression, in combination with caffeine, elicited pronounced behavioral stimulation. At higher doses of ADO and PAP, caffeine antagonized their depressant effects whereas at the lower doses of ADO and PAP in combination with caffeine there was behavioral stimulation. These results suggest there is a complex behavioral interaction between methylxanthines and central purinergic systems.