Inhibition by L-3,4-dihydroxyphenylalanine of hippocampal CAI neurons withfacilitation of noradrenaline and gamma-aminobutyric acid release

Electrophysiological studies were performed to elucidate whether L-3,4-dihy droxyphenylalanine (L-DOPA) acted on hippocampal CA1 neurons, since this dr ug has been reported to act as a neurotransmitter in the hypothalamus and s triatum. Hippocampal slices (450 (mum thick) obtained from male Wistar rats (4-7 weeks of age) were placed in a bath (maintained at 30 +/- 1 degreesC) continuously perfused with artificial cerebrospinal fluid. The population spikes elicited by electrical stimuli applied to the Schaffer collateral/co mmissural fibers were recorded in the hippocampal CAI region, using a glass micropipette filled with 3 M NaCl. Drugs were applied in the bath through a perfusion system. The population spikes were inhibited by L-DOPA (1 nM-10 muM) with a bell-shaped concentration-response curve (n = 7-15). Maximum i nhibitory effects were obtained at 100 nM. L-DOPA cyclohexyl ester, a putat ive L-DOPA recognition site antagonist, antagonized the L-DOPA-induced inhi bition of population spike. However, the inhibition remained unaffected in the presence of 3-hydroxybenzylhydrazine, an aromatic amino acid decarboxyl ase inhibitor. Furthermore, bath application of either phentolamine. an alp ha -adrenoceptor antagonist, or bicuculline, a GABA, receptor antagonist, a ntagonized the inhibitory effects of L-DOPA on population spikes. In additi on, bicuculline (1 (muM) antagonized the inhibition of population spike ind uced by 6-fluoronorepinephrine (10 muM). an alpha -adrenoceptor agonist, wh ile phentolamine(10 muM) did not affect the muscimol(1 muM)-induced inhibit ion. These results suggested that L-DOPA itself acted on L-DOPA recognition sites to release noradrenaline, and that the latter facilitates gamma -ami nobutyric acid (GABA) release via alpha -adrenoceptors located on the GABA- containing cells and/or their nerve terminals, thereby inhibiting the popul ation spikes in the hippocampal CA1 field. (C) 2001 Published by Elsevier S cience B.V.