Effect of alterations in extracellular norepinephrine on adrenoceptors: a microdialysis study in freely moving rats

Chronic electroshock treatment (once daily for 12 days) increases extracell ular norepinephrine in the frontal cortex and hippocampus as measured by mi crodialysis. This chronic treatment produced an elevation of basal norepine phrine overflow into extracellular space while both the first and the twelf th treatments produced a transient increase in norepinephrine overflow of a bout 40 min, Acutely, desmethylimipramine (10 mg/kg) treatment significantl y increased extracellular norepinephrine. While chronic desmethylimipramine (once daily for 10 days) increased basal overflow of norepinephrine in the frontal cortex and hippocampus, the tenth daily administration of desmethy limipramine did not produce a statistically significant increase in extrace llular norepinephrine. Both daily electroshock and daily desmethylimipramin e produced down regulation of beta-adrenoceptors in the hippocampus and the frontal cortex. Chronic electroshock caused up regulation of alpha-adrenoc eptors in the frontal cortex but not in the hippocampus while chronic desme thylimipramine administration did not alter alpha-adrenoceptors in either s tructure. Depletion of norepinephrine with reserpine or with 6-hydroxydopam ine prevented the down regulation of beta-adrenoceptors while depletion of this neurotransmitter did not prevent the electroshock-induced up regulatio n of alpha-adrenoceptors in the frontal cortex. These data suggest that dow n regulation of beta-adrenoceptors is mediated through increases in extrace llular norepinephrine. In contrast, up regulation of alpha-adrenoceptors ap pears to be independent of norepinephrine release and does not require the presence of noradrenergic neurons in order to be induced by electroshock. ( C) 1999 Elsevier Science B.V. All rights reserved.