A₁ adenosine receptor modulation of chemically and electrically evoked lumbar locomotor network activity in isolated newborn rat spinal cords.

It is not well-studied how the ubiquitous neuromodulator adenosine (ADO) affects mammalian locomotor network activities. We analyzed this here with focus on roles of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)-sensitive A(1)-type ADO receptors. For this, we recorded field potentials from ventral lumbar nerve roots and electrically stimulated dorsal roots in isolated newborn rat spinal cords. At ≥ 25μM, bath-applied ADO slowed synchronous bursting upon blockade of anion-channel-mediated synaptic inhibition by bicuculline (20 μM) plus strychnine (1 μM) and this depression was countered by DPCPX (1 μM) as tested at 100 μM ADO. ADO abolished this disinhibited rhythm at ≥ 500 μM. Contrary, the single electrical pulse-evoked dorsal root reflex, which was enhanced in bicuculline/strychnine-containing solution, persisted at all ADO doses (5 μM-2 mM). In control solution, ≥ 500 μM ADO depressed this reflex and pulse train-evoked bouts of alternating fictive locomotion; this inhibition was reversed by 1 μM DPCPX. ADO (5 μM-2 mM) did not depress, but stabilize alternating fictive locomotion evoked by serotonin (10 μM) plus N-methyl-d-aspartate (4-5 μM). Addition of DPCPX (1μM) to control solution did not change either the dorsal root reflex or rhythmic activities indicating lack of endogenous A(1) receptor activity. Our findings show A(1) receptor involvement in ADO depression of the dorsal root reflex, electrically evoked fictive locomotion and spontaneous disinhibited lumbar motor bursting. Contrary, chemically evoked fictive locomotion and the enhanced dorsal root reflex in disinhibited lumbar locomotor networks are resistant to ADO. Because ADO effects in standard solution occurred at doses that are notably higher than those occurring in vivo, we hypothesize that newborn rat locomotor networks are rather insensitive to this neuromodulator.