In vivo microdialysis reveals that blockade of accumbal orexin OX2 but not OX1 receptors enhances dopamine efflux in the nucleus accumbens of freely moving rats.
Eur J Neurosci
; 55(3): 733-745, 2022 02.
Article
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| MEDLINE
| ID: mdl-34989064
ABSTRACT
The nucleus accumbens contain orexinergic neural inputs and orexin OX1 - and OX2 -receptors. Behavioural studies suggest that accumbal orexin receptors modulate accumbal dopaminergic activity-dependent locomotion in rats. We studied the effects of intra-accumbal injection of orexin receptor ligands on accumbal extracellular dopamine levels in freely moving rats, using in vivo microdialysis and analysed the roles of OX1 - and OX2 -receptors in the regulation of basal accumbal dopamine efflux. The orexin receptor ligands were applied intra-accumbally though a microinjection needle attached with a dialysis probe. Neither the nonselective OX1 - and OX2 -receptor agonist orexin-A nor the preferential OX2 -receptor agonist orexin-B (500.0 pg and 5.0 ng) altered accumbal dopamine levels. The nonselective OX1 - and OX2 -receptor antagonist MK-4305 (suvorexant, 500.0 pg, 2.5 and 5.0 ng) enhanced dopamine efflux. A 2-h tetrodotoxin infusion into nucleus accumbens through the probe or co-administration of orexin-A (500.0 pg) strongly inhibited MK-4305 (5.0 ng)-induced accumbal dopamine efflux. The selective OX2 -receptor antagonist EMPA (90.0 and 900.0 pg, 9.0 ng) increased dopamine efflux. Intra-accumbal infusion of tetrodotoxin abolished EMPA (9.0 ng)-induced dopamine efflux. The selective OX1 -receptor antagonist SB-334867 (10.0 and 20.0 ng) failed to alter dopamine efflux. Co-administration of orexin-B (500.0 pg) inhibited both EMPA (9.0 ng)- and MK-4305 (5.0 ng)-induced dopamine efflux. Intraperitoneal injection of MK-4305 (10.0 mg/kg) did not affect accumbal dopamine efflux. The present study provides in vivo neuropharmacological evidence that accumbal OX2 - but not OX1 -receptors exert inhibitory regulation of basal accumbal dopamine efflux and that blockade of accumbal OX2 -receptors enhances dopamine efflux in nucleus accumbens of freely moving rats.
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MEDLINE
Asunto principal:
Dopamina
/
Núcleo Accumbens
Límite:
Animals
Idioma:
En
Año:
2022
Tipo del documento:
Article