Rauwolscine potentiates the effect of desipramine on limbic noradrenaline efflux

Desipramine, like most antidepressants, does not exert clinical benefit until 2-3 weeks after the onset of treatment. It has been suggested that this delay might be due to enhanced autoreceptor activation, counteracting the acute uptake blockade. We therefore tested whether autoreceptor blockade might enhance the response to acute uptake blockade, using voltammetry at carbon fibre microelectrodes to monitor stimulated noradrenaline (NA) efflux in rat bed nucleus of stria terminalis brain slices. Desipramine significantly increased NA efflux and slowed NA uptake. The combination of rauwolscine and desipramine increased NA efflux significantly more than desipramine alone. We suggest that alpha 2 autoreceptor blockade functionally mimics alpha 2 autoreceptor down-regulation and thus may allow the full therapeutic effect of desipramine to be manifested more rapidly.