- Release of dopaminein the nucleusaccumbons(N.Acc)is associated with motivationand hedonia,and an interactionbetweenthe dopaminergic and serotonergicsystems has been established.However, the commonhypothesesfor the etiologyof depressionare not concerned withthe releaseof dopanrinein the N.Accbut mostlywithalterationsin serotoninandnorepinephrinneurotransmission. In thisstudy,the in-vivo microdialysis technique was used to assess dopamine release and metabolismin the N.Acc of the FlindersSensitiveLine (FSL) rat, a proposedgeneticanimal modelof depression,as comparedto normal Sprague-Dawleyrats. Tissue contentand extracellularlevels of dopamine and its metabolizes(HVAand DOPAC)were determinedby an HPLCapparatuscoupledto an electrochemicaldetector.We foundthat the tissue contentof dopaminein the N.Accof FSLrats was six times higher than in controlrats. Nevertheless,basal extmcelhdardopamine levelsin the N.Accof the “depressed”rats were41.2 t 7.1%lowerthan thoseof controlrats. Whenthe N.Accof normalrats was perfusedwith serntonin(0.5pM)via thernicmdialysisprobe,the extracelhdarlevelsof dopamineand HVA were increasedby 228 z 38% and 122 f 5%, respectively.However,inFSLrats,noeffectof serotoninonextracelhdar levelsof dopaminewasobserved,whileextracellularlevelsof HVAand DOPACweresignificantlydecreased.Theseresultssuggestthatdepressive disorder might be associated with the inability of serotoninto stimulatedopaminereleasein the N.Acc,thereforeleadingto arrhcdonia and lack of motivation.