Increase of dopamine and norepinephrine release in the bed nucleus of stria terminalis: a common feature of antidepressants?

The bed nucleus of stria teminalis (BNST) is an area that is considered part of the extended amygdala, a complex involved in the acquisition and expression of emotions. BNST, is richly innervated by monoamines, sends projections back to monoamine neurons and is considered a relay station in mediating the activation stress response through a strict relationship with the hypothalamic-pituitary-adrenocortical axis (HPA). On the other hand chronic stress is considered a risk factor for developing depression. Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. Since the systemic administration of reboxetine, a selective norepinephrine transporter (NET) blocker increases the extracellular concentration (output) of norepinephrine (NE) but also of dopamine (DA) in the BNST, it is conceivable that catecholamine transmission in BNST could be involved in the mechanism of action of antidepressants. The aim of this study was to characterize the acute effect of antidepressants belonging either to the NET blockers category or to the 5-HT reuptake blockers category (SSRI) on DA and NE ouput in the BNST, assayed through the in vivo microdialysis technique. The results obtained show that all the tested antidepressants (5 to 20 mg/kg i.p.) increased, dose dependently, NE and DA in the BNST. In particular, the increase reported for NE and DA respectively in % over basal were were as follows: desipramine, 239 and 137; reboxetine 185 and 128; imipramine 512 and 359; citalopram 95 and 122; fluoxetine 122 and 68; bupropion 255 and 164. Furhtermore, reboxetine, citalopram and the selective DA reuptake inhibitor GBR12909 infused locally in the BNST, through the dialysis fiber increase in a different manner catecholamine release in the BNST. These results suggest that catecholamine transmission in the BNST might be a common downstream pathway that is involved in the mechanism of action of antidepressants and consequently it can be hypothesized that a dysfunction of neuronal transmission in this brain area might have a role in the aetiology of affective disorders. On these bases it can be also suggested that modulation of catecholamine transmission in the BNST can be utilized in the screening process of new antidepressant