INCREASED NEOSTRIATAL TYROSINE HYDROXYLATION DURING STRESS - ROLE OF EXTRACELLULAR DOPAMINE AND EXCITATORY AMINO-ACIDS

We examined the regulation of neostriatal tyrosine hydroxylation durin g acute stress, testing the hypothesis that excitatory amino acids (EA As) contribute to the stress-evoked increase in dopamine (DA) synthesi s. Dialysis probes implanted into neostriatum permitted delivery of dr ugs and sampling of extracellular fluid, Rats were exposed to 30 min o f intermittent tail shock during infusion of an inhibitor of aromatic amino acid decarboxylase (AAAD), NSD-1015 (100 mu M), and DOPA was mea sured in the dialysate. Tail shock was applied beginning either 15 min after the onset of NSD-1015 treatment (the initial rate of DOPA accum ulation) or 75 min after the onset of treatment (when DOPA had approac hed steady state). Tail shock increased the steady-state levels of ext racellular DOPA in neostriatum (+40%), However, there was no change in the initial rate of DOPA accumulation unless animals also received th e D-2 receptor antagonist eticlopride (50 nM), in which case an increa se was observed (+228%). The impact of tail shock on the steady-state level of DOPA was attenuated by the D-2 agonist quinpirole (100 mu M), or by 2-amino-5-phosphonovalerate (APV) (100 mu M) or 6-cyano-7-nitro quinoxaline-2,3-dione (CNQX) (100 mu M), EAA antagonists acting at NMD A or -amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) recepto rs, respectively. These data suggest that acute stress normally has li ttle effect on tyrosine hydroxylation in neostriatum due to the inhibi tory influence of DA in the extracellular fluid. However, when that in fluence is absent (e.g., during extended inhibition of DOPA decarboxyl ation or blockade of DA receptors), stress increases tyrosine hydroxyl ation via EAAs acting on NMDA and AMPA receptors. Thus, EAAs released from corticostriatal projections may stimulate DA synthesis and thereb y restore dopaminergic activity under conditions in which the availabi lity of DA for release has been compromised.