LOCAL INFLUENCE OF ENDOGENOUS NOREPINEPHRINE ON EXTRACELLULAR DOPAMINE IN RAT MEDIAL PREFRONTAL CORTEX

Noradrenergic and dopaminergic projections converge in the medial pref rontal cortex and there is evidence of an interaction between dopamine (DA) and norepinephrine (NE) terminals in this region, We have examin ed the influence of drugs known to alter extracellular NE on extracell ular NE and DA in medial prefrontal cortex using in vivo microdialysis . Local application of the NE uptake inhibitor desipramine (1.0 mu M) delivered through a microdialysis probe increased extracellular DA (149%) as well as NE (+ 201%) in medial prefrontal cortex, Furthermore, desipramine potentiated the tail shock-induced increase in both extra cellular DA (stress alone, + 64%; stress + desipramine, + 584%) and NE (Stress alone, + 55%; stress + desipramine, + 443%). In contrast, loc al application of desipramine did not affect extracellular DA in stria tum, indicating that this drug does not influence DA efflux directly. Local application of the alpha(2)-adrenoceptor antagonist idazoxan (0. 1 or 5.0 mM) increased extracellular NE and DA in medial prefrontal co rtex, Conversely, the alpha(2)-adrenoceptor agonist clonidine (0.2 mg/ kg; i.p,) decreased extracellular NE and DA in medial prefrontal corte x. These results support the hypothesis that NE terminals in medial pr efrontal cortex regulate extracellular DA in this region. This regulat ion may be achieved by mechanisms involving an action of NE on recepto rs that regulate DA release (heteroreceptor regulation) and/or transpo rt of DA into noradrenergic terminals (heterotransporter regulation).