Publication: Canadian Journal of Physiology and Pharmacology • 18 April 2012 • https://doi.org/10.1139/y2012-045
Granule matrix property and rapid “kiss-and-run” exocytosis contribute to the different kinetics of catecholamine release from carotid glomus and adrenal chromaffin cells at matched quantal size
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Venlafaxine is recognised as an effective treatment for depression and is known to inhibit the reuptake of serotonin (5-HT) and noradrenaline (NA). Another antidepressant, bupropion, acts to inhibit dopamine (DA) and NA reuptake and is commonly co-administered with other antidepressants to improve the efficacy of the antidepressant effect. The present study was designed to investigate the acute effect of combining the 2 drugs on extracellular levels of 5-HT, DA, and NA in rat frontal cortex using brain microdialysis, with the drugs being administered by intraperitoneal injection (i.p). Bupropion (10 mg/kg body mass, i.p.) alone had no effect on extracellular 5-HT levels, whereas venlafaxine (10 mg/kg, i.p.) alone significantly elevated extracellular 5-HT over basal values. As expected, bupropion alone elevated extracellular dopamine above basal values at 40 min post-drug administration, and this effect lasted for a further 2 h. Venlafaxine alone did not statistically elevate extracellular dopamine. The co-administration of venlafaxine with bupropion resulted in a dramatic increase in extracellular dopamine, and this effect was significantly greater than that seen with bupropion alone. In the frontal cortex, NA was elevated by bupropion alone and venlafaxine alone, relative to the control animals. The combination of bupropion and venlafaxine resulted in a marked elevation of NA.

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La venlafaxine est reconnue pour traiter efficacement la dépression et est connue pour inhiber la recapture de la sérotonine (5-HT) et de la noradrénaline (NA). Un autre antidépresseur, le bupropion, agit pour inhiber la recapture de dopamine (DA) et de NA et est souvent administré conjointement à d’autres antidépresseurs pour améliorer l’efficacité de l’effet antidépresseur. L’étude présente a été conçue pour examiner l’effet aigu de combiner les deux médicaments sur les niveaux extracellulaires de 5-HT, de DA et de NA dans le cortex frontal du rat en utilisant une microdialyse cérébrale, les médicaments ayant été administrés par voie intrapéritonéale (i.p.). Le bupropion (10 mg/kg de poids corporel, i.p.) seul n’avait pas d’effet sur les niveaux de 5-HT extracellulaires, alors que la venlafaxine (10 mg/kg, i.p.) seule élevait de manière significative les niveaux de 5-HT extracellulaires au-dessus des valeurs de base. Tel qu’attendu, le bupropion seul élevait les niveaux extracellulaires de dopamine au-dessus des valeurs de base, 40 minutes après son administration et cet effet perdurait pendant 2 heures additionnelles. La venlafaxine seule n’élevait pas significativement les niveaux de dopamine extracellulaire. L’administration conjointe de venlafaxine et de bupropion accroissait nettement la dopamine extracellulaire et cet effet était significativement plus important que celui du bupropion seul. La NA du cortex frontal était accrue par le bupropion seul et par la venlafaxine seule par rapport aux animaux contrôles. La combinaison de bupropion et de venlafaxine résultait en une élévation marquée de NA.
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