The effect of fluvoxamine and sertraline on the opioid withdrawal syndrome: a combined in vivo cerebral microdialysis and behavioural study.
A microdialysis study was undertaken to determine the effect of acute and sub-chronic administration of the selective serotonin reuptake inhibitor, fluvoxamine, and the acute effect of the selective serotonin reuptake inhibitor sertraline, on the naloxone precipitated opioid withdrawal induced increase in hippocampal noradrenaline levels. This study also determined the effect of fluvoxamine and sertraline on opioid withdrawal-induced physical behaviours. Naloxone (1 mg kg(-1); i.p.) increased noradrenaline levels in the hippocampus of morphine dependent rats 20 min after administration, with peak levels of 267+/-13% of baseline, occurring 40 min after administration of naloxone. Opioid withdrawal-induced physical behaviours were evident in morphine dependent rats 5 min after a naloxone injection (1 mg kg(-1); i.p.). Acute fluvoxamine or sertraline (10 mg kg(-1); i.p.) given 40 min before naloxone (1 mg kg(-1); i.p.) did not modify the increased hippocampal noradrenaline levels (242+/-15 and 242+/-19%, respectively), observed in morphine dependent rats following an naloxone injection. Acute fluvoxamine and sertraline (10 mg kg(-1); i.p.) reduced the severity of the naloxone precipitated opioid withdrawal syndrome. Sub-chronic treatment with fluvoxamine (10 mg kg(-1); i.p.) prevented the naloxone precipitated increase in hippocampal noradrenaline levels in morphine dependent rats. Furthermore, sub-chronic fluvoxamine produced a significantly reduced baseline level of noradrenaline in these rats which was 52.5+/-8% of baseline 40 min after naloxone.
Gray
Alex M
AM
University Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford OX12 6HE, UK. amg5818@gsk.com
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D016666:Fluvoxamine / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis / Q000379:methods; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D000701:Analgesics, Opioid; D004338:Drug Combinations; D016666:Fluvoxamine; D009020:Morphine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline