Norepinephrine but not serotonin reuptake inhibitors enhance theta and gamma activity of the septo-hippocampal system

Abstract

Current neurobiologicalconcepts attribute a centralrole of the hippocampalformation in cognitive and affective processes. Recent studies indicate that the hippocampus is affected in human depression, and antidepressant drugs induce hippocampaladaptive changesthat are thought to be associated with theirtherapeutic action. In the present study, we investigated the action of various antidepressantdrugs on the activity of the septo-hippocampalsystem, its oscillatory activity in particular. The acute effects of the norepinephrine (NE)reuptake inhibitors reboxetine and desipramine, and the selective serotonin reuptake inhibitorfluvoxamine were evaluated. Extracellular single-unit recordings were performed from the medialseptum/diagonalband of Broca (MS/DBv), with simultaneous hippocampalEEGrecordings of anesthetized rats. Systemic administration of reboxetine synchronized hippocampalEEG, resulting in a significant increase inpower at theta frequency, and an increase in frequency and power of gamma-wave activity. Parallelto EEG synchrony, reboxetineinduced orenhanced theta oscillation of MS/DBv neurons. Oscillatory frequencies of MS/DBv neurons were identical, and phase lockedto the corresponding hippocamapaltheta frequencies. Under the same experimental conditions, reboxetine induced a two-fold increasein extracellular NE (but not serotonin) levels in the hippocampus as revealed by microdialysis. Desipramine, but not the serotoninreuptake inhibitorfluvoxamine, evoked responses similarto those of reboxetine regarding septo-hippocampaltheta activity. The presentfindings indicate that even though both NE and serotonin reuptake inhibitors are clinically effective antidepressant drugs, their action onthe septo-hippocampaloscillatory behavior is different. It is presumed that selective NE reuptake inhibitors could modulate variouscognitive processes associated with hippocampaloscillatory activity. © 2003 American College of Neuropsychopharmacology.