ANTICONVULSANT ACTIVITY OF THE NORADRENERGIC LOCUS-CERULEUS SYSTEM - ROLE OF BETA-MEDIATION

Many experimental observations have demonstrated the modulatory role e xerted by several neural structures and neurotransmitters on spontaneo us and paroxysmal bioelectric activity of the hippocampus. Recently, t he control exerted by locus coeruleus (LC) and its noradrenergic (NA) efferent pathway on different experimental models of epilepsy (e.g. co rtical cobalt chronic epilepsy, amygdaloid and hippocampal kindling) w as emphasised. On this basis, a series of experiments was performed to elucidate the functional role of LC-NA system on the hippocampal peni cillin (PCN) focus and the type of adrenergic receptor involved. The e xperiments were carried out on 25 rats in which an epileptiform hippoc ampal focus was obtained through intrahippocampal PCN administration ( 100-200 I.U.). In these conditions, LC, ipsilateral to PCN hippocampal focus, was stimulated before and after intraperitoneal (i.p.) adminis tration of a beta-adrenergic receptor antagonist propranolol (2 mg/kg) . Results showed a significant reduction of hippocampal spiking freque ncy during LC stimulation; after i.p. propranolol injection, LC stimul ation, at the same parameters, failed to induce any sort of modificati on of PCN hippocampal spiking frequency. Furthermore, intrahippocampal application of a beta-selective agonist 2-fluoro-noradrenaline (2-FNA ) mimics the inhibitory effects of LC stimulation. All data suggest th at the LC-NA system is able to induce a net reduction of hippocampal e pileptiform focus and the inhibitory NA control involves the activatio n of adrenergic beta receptors.