MODULATION OF IN-VIVO STRIATAL TRANSMITTER RELEASE BY NITRIC-OXIDE AND CYCLIC-GMP

The effects of nitric oxide (NO) and cyclic GMP on in vivo transmitter release in the rat striatum were investigated using microdialysis sam pling in urethane-anaesthetised animals. The NO release-inducing subst ances S-nitrosoacetylpenicillamine (SNAP), S-nitrosoglutathione (SNOG) , and sodium nitroprusside (SNP) increased extracellular concentration s of aspartate (Asp), glutamate (Glu), gamma-aminobutyric acid (GABA), taurine (Tau), acetylcholine (ACh), and serotonin (5-HT). Dopamine (D A) concentrations were decreased by SNAP but were increased by SNOG an d SNP. An NO scavenger, haemoglobin, blocked or reduced the effects of SNAP on transmitter release. However, the control carrier compounds f or SNAP, SNOG, and SNP (penicillamine, glutathione, and potassium ferr icyanide, respectively, which do not induce release of NO) also increa sed GABA, Tau, DA, and 5-HT concentrations. When NO gas was given dire ctly by dissolving it in degassed Ringer's solution, DA concentrations decreased significantly, and those of Asp, Glu, GABA, Tau, ACh, and 5 -HT increased. These effects of NO gas were all inhibited by coadminis tration of haemoglobin and for GABA, Tau, ACh, and DA showed some calc ium dependency. The cyclic GMP agonists 8-bromo-cyclic GMP and dibutry l-cyclic GMP stimulated dose-dependent increases in Asp, Glu, GABA, Ta u, ACh, DA, and 5-HT concentrations. Increased striatal transmitter re lease in response to NO may therefore be mediated by its stimulatory a ction on cyclic GMP formation. NO inhibition of DA release may be medi ated indirectly through its stimulation of local cholinergic and GABAe rgic neurones.