Oxazepam and temazepam attenuate paroxetine-induced elevation of serotonin levels in guinea-pig hippocampus.
Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are used as a first-line treatment in depression. However, many depressed patients are also treated with benzodiazepines to alleviate increased anxiety and sleep disturbances normally associated with depression. Since benzodiazepines inhibit 5-HT neuronal firing activity, they might attenuate SSRI-induced increase in extracellular 5-HT levels. This study aimed to assess, using in-vivo microdialysis, the effects of the benzodiazepines oxazepam or temazepan on the SSRI paroxetine-induced 5-HT increase in the hippocampus of freely moving guinea-pigs. It was found that the acute systemic administration of paroxetine increased extracellular 5-HT levels. Pre-administration of oxazepam or temazepam significantly diminished the paroxetine-induced elevation of extracellular 5-HT levels (from 350% to 200% of baseline). It was concluded that benzodiazepines attenuate the ability of SSRIs to elevate hippocampal 5-HT levels. Thus, co-administration of benzodiazepines might affect the therapeutic efficacy of SSRI treatment.
Cremers
Thomas I F H
TI
Department of Biomonitoring & Sensoring, University of Groningen Institute of Pharmacy, Groningen, The Netherlands.
Dremencov
Eliyahu
E
Bosker
Fokko J
FJ
Westerink
Ben H C
BH
D000704:Analysis of Variance; D000818:Animals; D004347:Drug Interactions; D018757:GABA Modulators / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D010076:Oxazepam / Q000494:pharmacology*; D017374:Paroxetine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013693:Temazepam / Q000494:pharmacology*; D013997:Time Factors
D018757:GABA Modulators; D010076:Oxazepam; D017374:Paroxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013693:Temazepam