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Cellular electrophysiological effects of chronic fluoxetine and duloxetine administration on serotonergic responses in the aging hippocampus
Author(s) -
Smith Jane E.,
Lakoski Joan M.
Publication year - 1998
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199811)30:3<318::aid-syn9>3.0.co;2-e
Subject(s) - duloxetine , serotonergic , fluoxetine , reuptake inhibitor , serotonin , duloxetine hydrochloride , hippocampus , serotonin reuptake inhibitor , pharmacology , antidepressant , medicine , endocrinology , reuptake , raphe nuclei , anesthesia , chemistry , receptor , alternative medicine , pathology
The pharmacological and physiological effects of chronic administration of the selective serotonin (5‐hydroxytryptamine, 5‐HT) reuptake inhibitor (SSRI) fluoxetine and the dual 5‐HT/norepinephrine (NE) reuptake inhibitor duloxetine were compared on 5‐HT‐mediated electrophysiological responses recorded in the hippocampus of young (3–5 months) and old (17–20 months) female Fischer 344 rats. Fluoxetine, duloxetine, or vehicle (saline) was administered once daily for 14 days (10 mg/kg, i.p.) and extracellular recordings of spontaneously firing CA1 and CA3 pyramidal neurons were conducted 24 h following the last injection using microiontophoretic drug application techniques in a chloral hydrate anesthetized preparation. The recovery times (RT 50 values; sec) following 5‐HT application on pyramidal neurons were significantly increased in the young and old chronic fluoxetine (FLX) treated groups (73% and 104%, respectively; P < 0.05), but not chronic duloxetine‐ (DLX) or vehicle‐ (VEH) treated groups. Following prolonged application of duloxetine (5–10 min), the 5‐HT RT 50 values were significantly increased in the young FLX groups as compared to the age‐matched DLX‐ and VEH‐treated groups. In contrast, a significant decline in the time to recovery produced by 5‐HT (52%) was observed in the old vs. young FLX‐treated group following the second co‐application of 5‐HT with duloxetine. Within each drug treatment and age group, co‐application of duloxetine and 5‐HT did not alter the inhibitory responses (IT 50 values; nC) produced by the application of 5‐HT alone. These results demonstrate cellular adaptive changes in serotonergic neuronal function occur following repeated exposure to 5‐HT reuptake inhibitors in an age‐dependent manner. Synapse 30:318–328, 1998. © 1998 Wiley‐Liss, Inc.