Effect of antidepressants and adolescent stress on catecholamine transmission in the rat bed nucleus of stria terminalis (BNST): a microdialysis study

Rationale: Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. The bed nucleus of stria terminalis (BNST) is considered a relay station in mediating the activation of stress response but also in the acquisition and expression of emotions. Chronic stress, particularly at developmental stage, has long-lasting deleterious effects on several cortico-limbic areas. Abnormal catecholamine transmission in the BNST evoked by chronic stress exposition at peri-adolescent age may be interpreted as relevant neurochemical marker at the onset of adolescent or adult depression. BNST is richly innervated by monoamines and sends back projections to the nucleus of origin. We previously showed that the administration of selective blockers of norepinephrine transporter (NET) increases the extracellular concentration (output) of dopamine, suggesting that dopamine could be captured by NET in the BNST. Among new experimental strategies investigated for the theraphy of depression, the treatment with sub-anesthetic doses of ketamine has been suggested to be one of the most promising. Objectives: The aims of this study, carried out by means of in vivo microdialysis, were: (i) ascertain the acute effects that antidepressants with varying mechanisms of action have on dopamine and norepinephrine output in the BNST; (ii) ascertain the acute effects that sub-anesthetic doses of ketamine have on dopamine and norepinephrine output in the BNST; (iii) ascertain whether peri-adolescent unpredictable chronic stress could produce changes in dopamine and norepinephrine transmission in the BNST. Results: We observed the following: (i) all the antidepressants tested (5-20 mg/Kg i.p.) increased the output of catecholamines, dose dependently; (ii) ketamine (10-40 mg/Kg i.p.) increased the output of catecholamines, dose dependently; (iii) peri-adolescent unpredictable chronic stress determined changes of basal and stimulated catecholamine output. Conclusions: These results suggest that catecholamine transmission in the BNST may be part of a common downstream pathway that is involved in the action mechanism of antidepressants, and in the effects of stress. Consequently, it is hypothesized that a dysfunction of neuronal transmission in this brain area may have a role in the etiology of affective disorders.