Norepinephrine-stimulated cyclic AMP accumulation in brain slices in vitro after serotonin depletion or chronic administration of selective amine reuptake inhibitors.

These experiments demonstrate that altering serotonin availability in vivo does not influence the interaction of norepinephrine with adenylate cyclase in vitro. Neither reducing serotonin levels (parachloroamphetamine) nor increasing the availability of serotonin by blocking its reuptake (fluoxetine) affect the norepinephrine-induced elevation of cyclic AMP in slices of the limbic forebrain of rats. However, increasing norepinephrine availability by chronic administration of desipramine, a norepinephrine reuptake inhibitor, reduces cyclic AMP synthesis in the limbic forebrain. However, it is doubtful that blockade of norepinephrine reuptake alone accounts for the reduction in receptor sensitivity produced by desipramine since chronic administration of a new norepinephrine reuptake inhibitor, nisoxetine, does not decrease cyclic AMP accumulation.