Antidepressants, dose dependently, increase dopamine and norepinephrine extracellular concentration in rat bed nucleus of stria terminalis: a microdialysis study

The bed nucleus of stria teminalis (BNST) is an area that has been considered part of the extended amygdala, a complex involved in the acquisition and expression of emotions that shares with the nucleus accumbens shell the sensitivity of dopamine (DA) transmission to drugs of abuse and with the prefrontal cortex (PFCX) a consistent noradrenergic innervation. The systemic administration of a selective norepinephrine transporter (NET) blocker determines an increase of DA extracellular concentration in the BNST, an effect previously observed in the PFCX, that is likely due to the blockade of a non specific reuptake of DA by NET. On the other hand the administration of a selective a dopamine reuptake (DAT) blocker determines a strong increase of extracellular DA concentration similarly to that observed in the NAcc accumbens shell (Carboni et al. J. Neurochem. 96, 473, 2006). The aim of this study was to characterize the effect of antidepressants belonging to NET blockers category or 5-HT reuptake blockers on DA and norepinephrine (NE) extracellular concentration in the BNST, evaluated through in vivo microdialysis. The results obtained show that all antidepressant tested increased, dose dependently, DA and NE extracellular concentration in the BNST. In particular, imipramine at doses ranging from 5 to 20 mg/kg ip increased DA ( from 100 to 400 % over basal) and NE (from 100 to 400 % over basal); desipramine at doses ranging from 5 to 20 mg/kg ip increased DA ( from 115 to 225 % over basal) and NE (from 50 to 200 % over basal); reboxetine at doses ranging from 5 to 20 mg/kg ip increased DA (up to 100 % over basal) and NE (up to 150 % over basal); atomoxetine at doses ranging from 1 to 10 mg/kg ip increased DA ( up to 110 % over basal) and NE (up to 150 % over basal); citalopram at doses ranging from 5 to 20 mg/kg ip increased DA ( up to 75 % over basal) and NE (up to 185 % over basal). These results suggest that the increase of DA extracellular concentration in BNST, induced by antidepressants, might be due to the blockade of the non specific DA reuptake through NET but also to a mechanism the involves extra BNST circuits that are activated by 5-HT extracellar increase due to 5-HT reuptake blockade. In conclusion this study suggests that NE and DA transmission in BNST might play an important role in the therapeutic effect of antidepressants and in the etiology of affective disorders