Cellular electrophysiological effects of chronic fluoxetine and duloxetine administration on serotonergic responses in the aging hippocampus
✍ Scribed by Jane E. Smith; Joan M. Lakoski
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 275 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0887-4476
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✦ Synopsis
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 Ͻ 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.