Increased striatal dopamine efflux in vivo following inhibition of cerebral nitric oxide synthase by the novel monosodium salt of 7‐nitro indazole

Abstract

The role of nitric oxide (NO) in striatal dopamine release has been controversial. Most NO synthase inhibitors affect more than one isoform of the enzyme and exert vasoconstrictor effects which may also affect striatal dopamine function. We now report on the effect of a soluble monosodium salt of the selective brain NO synthase inhibitor 7-nitro indazole (7-NINA). Using 7-NINA the first study of selective inhibition of the brain isoform of NO synthase on dopamine efflux in rat striatum was undertaken by use of in vivo microdialysis. Perfusion with 7-NINA (1 mM) increased striatal dopamine efflux. The effect of 7-NINA was partially antagonized (67%) by co-perfusion with L-arginine (1 mM), the precursor of NO formation in vivo. This suggests that 7-NINA induces a competitive inhibition of NO synthase activity. These data show that endogenous NO has an inhibitory effect on striatal dopamine efflux in vivo.

Gender-related differences in the effects of nitric oxide donors on neuroleptic-induced catalepsy in mice

“…It has been demonstrated in male mice that NOS inhibitors are able to induce catalepsy and also to potentiate neuroleptic-induced catalepsy (34), an effect that seems to involve serotonin receptors (35). To further emphasize the complexity of this topic, it should be mentioned that, under some circumstances, endogenous NO can decrease the release of dopamine (13,14). Nevertheless, the precise mechanisms involved in the modulation of dopamine release by NO (and NO donors) remain to be determined.…”

“…This influence is rather complex, since it can in-volve either dopamine release, uptake or metabolism (9). Some studies suggest that endogenous NO increases dopamine release in the striatum and other areas of the CNS (10)(11)(12), while other authors suggest the opposite (13,14). If NO increases the release of dopamine in the striatum, we would expect that drugs that release or are metabolized into NO (i.e., NO donors) are able to attenuate neuroleptic-induced catalepsy, which is mainly caused by blockade of striatal dopaminergic receptors (1).…”

Ultrastructural features of the nitric oxide synthase-containing interneurons in the nucleus accumbens and their relationship with tyrosine hydroxylase-containing terminals

“…A role for NO in the release of dopamine has been widely proposed (Zhu and Luo, 1992;Lonart et al, 1993;Guevara Guzman et al, 1994;Ishida et al, 1994;Silva et al, 1995). Furthermore, as gap junction permeability between medium-sized, densely spiny neurons can be modulated by dopamine in the nucleus accumbens (O'Donnell and Grace, 1993), and by NO in the dorsal striatum (O'Donnell and Grace, 1997), these inputs may act together to modulate activities of individual projection neurons by means of conventional chemical synapses, or may influence electrotonic transmission between networks of neurons connected by gap junctions.…”

“…In the dorsal striatum, NO interacts with dopamine (Hanbauer et al, 1992;Zhu and Luo, 1992;Lonart et al, 1993;Guevara Guzman et al, 1994;Ishida et al, 1994;Silva, et al, 1995;Shibata et al, 1996;West and Galloway, 1998) and other neurotransmitters (Guevara Guzman et al, 1994;Moller et al, 1995;Bogdanov and Wurtman, 1997;Hanania and Johnson, 1998;Ikarashi et al, 1998;Segovia and Mora, 1998). Little is known of the effects of NO in the nucleus accumbens, although it seems likely that the interactions between NO and various transmitters that occur in the dorsal striatum also take place in the nucleus accumbens.…”

Two types of interneurons in the cat visual thalamus are distinguished by morphology, synaptic connections, and nitric oxide synthase content

“…Whereas the release of ACh alone may trigger this switch in firing mode (Eysel et al, 1986;McCormick andPrince, 1986, 1987;Francesconi et al, 1988;McCormick and Pape, 1988;McCormick, 1989), NO released from PBR terminals, in addition, may modulate neurotransmitter release and receptor activation (Lonart et al, 1992;Lorrain and Hull, 1993;Guevara-Guzman et al, 1994;Strasser et al, 1994;Silva et al, 1995) or may influence more directly the membrane properties of thalamocortical cells (Pape and Mager, 1992;Cudeiro et al, 1994aCudeiro et al, ,b, 1996Murphy et al, 1994). Thus, the dual release of ACh and NO in the LGN may mediate a complex enhancement of thalamocortical cell responses.…”