Anticonvulsant A(1) receptor-mediated adenosine action on neuronal networks in the brainstem-spinal cord of newborn rats

Membrane potential of ventral respiratory group neurons as well as inspirat ory-related cranial (hypoglossal) and spinal (C-1-Th-4) nerve activities we re analysed in brainstem-spinal cord preparations from neonatal rats. Block of Cl--mediated inhibition with bicuculline (plus strychnine) affected nei ther rhythmic depolarizations nor spike discharge in 23 of 30 ventral respi ratory group cells. In the other seven neurons, block of inhibitory postsyn aptic potentials evoked pronounced depolarizations and spike discharge that was synchronous with seizure-like spinal nerve activity. Respiratory hypog lossal nerve activity persisted after transection at the spinomedullary jun ction, whereas spinal rhythm was blocked. After transection, the moderate b icuculline-evoked seizure-like perturbation of hypoglossal nerve activity w as abolished and rhythmic ventral respiratory group neuron activity was not disturbed, whereas epileptiform discharge persisted in spinal nerves. The seizure-like nerve activity and depolarization of the minor subpopulation o f perturbed ventral respiratory group neurons were reversed by either adeno sine or the A(1) adenosine receptor agonist 2-chloro-N-6-cyclopentyladenosi ne. The A(2) receptor agonist CGS 21860 had no effect, In control preparati ons, inspiratory nerve activity and membrane potential fluctuations (29 of 35 cells) were nor changed by adenosine, 2-chloro-N-6-cyclopentyladenosine or CGS 21860. In the other six cells, adenosine evoked a hyperpolarization (<10 mV) with no major change in input resistance. The anticonvulsant effec ts of adenosine and 2-chloro-N-6-cyclopentyladenosine were antagonized by t he A(1) adenosine receptor blocker 8-cyclopentyl-1,3-dipropylxanthine. Afte r pre-incubation with 8-cyclopentyl-1,3-dipropylxanthine, bicuculline also evoked seizure-like discharge in the hypoglossal nerve. The results indicate that seizure-like spinal motor output of the respirato ry network upon block of Cl--mediated inhibition is caused by disinhibition of spinal neuronal networks with afferent connections to the ventral respi ratory group. Presynaptic Al adenosine receptors exert an anticonvulsant ac tion on the disinhibited spinal motor network, but have no depressing effec t per se on the isolated medullary respiratory network. (C) 2000 IBRO. Publ ished by Elsevier Science Ltd.