Inhibition by L-3,4-dihydroxyphenylalanine of hippocampal CA1 neurons with facilitation of noradrenaline and gamma-aminobutyric acid release.

Electrophysiological studies were performed to elucidate whether L-3,4-dihydroxyphenylalanine (L-DOPA) acted on hippocampal CA1 neurons, since this drug has been reported to act as a neurotransmitter in the hypothalamus and striatum. Hippocampal slices (450 microM thick) obtained from male Wistar rats (4-7 weeks of age) were placed in a bath (maintained at 30+/-1 degrees C) continuously perfused with artificial cerebrospinal fluid. The population spikes elicited by electrical stimuli applied to the Schaffer collateral/commissural fibers were recorded in the hippocampal CA1 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 microM) with a bell-shaped concentration-response curve (n=7-15). Maximum inhibitory effects were obtained at 100 nM. L-DOPA cyclohexyl ester, a putative L-DOPA recognition site antagonist, antagonized the L-DOPA-induced inhibition of population spike. However, the inhibition remained unaffected in the presence of 3-hydroxybenzylhydrazine, an aromatic amino acid decarboxylase inhibitor. Furthermore, bath application of either phentolamine, an alpha-adrenoceptor antagonist, or bicuculline, a GABA(A) receptor antagonist, antagonized the inhibitory effects of L-DOPA on population spikes. In addition, bicuculline (1 microM) antagonized the inhibition of population spike induced by 6-fluoronorepinephrine (10 microM), an alpha-adrenoceptor agonist, while phentolamine (10 microM) did not affect the muscimol (1 microM)-induced inhibition. These results suggested that L-DOPA itself acted on L-DOPA recognition sites to release noradrenaline, and that the latter facilitates gamma-aminobutyric acid (GABA) release via alpha-adrenoceptors located on the GABA-containing cells and/or their nerve terminals, thereby inhibiting the population spikes in the hippocampal CA1 field.