Role of ionotropic glutamatergic receptors and nitric oxide in the effects of flutriafol, a triazole fungicide, on the <i>in vivo</i> striatal dopamine release

Abstract

-Flutriafol is a triazole fungicide that induces spontaneous and depolarization-stimulated release of dopamine from rat striatum, although the neurochemical mechanism by which this fungicide induces this effect is unknown. The purpose of the present work was to assess the implication of ionotropic glutamatergic receptors and nitric oxide (NO) production in the flutriafol-induced dopamine release from rat striatum. To this, we have used non-competitive antagonists of NMDA (dizocilpine, MK-801), and (AMPA)/kainate (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX) receptors, or nitric oxide synthase (NOS) inhibitors (Nomega-nitro-L-arginine -L-NARG -and 7-nitro-indazol -7-NI), to study the striatal dopamine release induced by flutriafol. Intrastriatal infusion of 6 mM flutriafol increased the dopamine levels to 984 ± 141%, with respect to basal levels. Infusion of flutriafol (6 mM) in MK-801 (500 μM) or CNQX (500 μM) pretreated animals, increased striatal dopamine levels to 489 ± 74% and 477 ± 78%, with respect to basal levels, respectively, these increases being 50.3% and 51.5% smaller than those induced by flutriafol in non-pretreated animals. Infusion of flutriafol (6 mM) in L-NARG (1 mM) or 7-NI (100 μM) pretreated animals, increased the extracellular dopamine levels to 400 ± 88.5 and 479 ± 69.4%, with respect to basal levels, respectively, these increases being 59.3 and 51% smaller than those induced by flutriafol in non-pretreated animals. In summary, flutriafol appears to act, at least in part, through an overstimulation of NMDA receptors with possible NO production to induce dopamine release, and the administration of NMDA and AMPA/kainate receptor antagonists and NOS inhibitors protects against flutriafol-induced dopamine release from rat striatum.

Participation of glutamatergic and nitrergic systems in the striatal dopamine release induced by isatin, a MAO inhibitor

“…The exception was the 7-NI, which significantly decreased the effect of isatin on DOPAC and HVA levels compared to the isatin group. This was an unexpected result since previous studies in our laboratory show that the administration of 100 μM 7-NI did not modify the levels of the metabolites (Campos et al, 2006;Faro et al, 2012Faro et al, , 2013. Considering that the primary metabolites source comes from the metabolism, through MAO, of the cytoplasmic dopamine pool (Gazzara & Andersen, 1994;Zetterström et al, 1986), we interpret these results as follows: considering isatin as an MAO inhibitor, its administration leads to a decrease in the metabolism of dopamine with a consequent increase in its levels and a decrease in the levels of its metabolites.…”

Acupuncture inhibition of methamphetamine‐induced behaviors, dopamine release and hyperthermia in the nucleus accumbens: mediation of group II mGluR

“…Dopaminergic neuronal activity can be regulated by glutamatergic neurotransmission, projecting from the prefrontal cortex to the VTA or NAc, via activation of ionotropic and metabotropic glutamate receptors (Tye, Miller & Blaha 2013;Johnson, Mateo & Lovinger 2017). It has been shown that intra-VTA infusion of AMPA enhanced basal NAc DA release (Tye et al 2013), and pretreatment with AMPA antagonist CNQX blocked flutriafol-induced DA release in the striatum (Faro et al 2012). In our preliminary experiment, either microinjection of an AMPA receptor antagonist CNQX into the VTA or electrolytic lesion of infralimbic cortex failed to block inhibitory effect of HT7 acupuncture on METH-induced NAc temperature, suggesting a lack of involvement of AMPA receptors (data not shown).…”