Fluoxetine, a selective inhibitor of serotonin uptake, potentiates morphine analgesia without altering its discriminative stimulus properties or affinity for opioid receptors
The analgesic effect of morphine in the rat tail jerk assay was enhanced by the serotonin uptake inhibitor, fluoxetine. Tail jerk latency was not affected by fluoxetine alone. Morphine's affinity for opioid receptors labeled in vitro with /sup 3/H-naloxone or /sup 3/H-D-Ala/sup 2/-D-Leu/sup 5/-enkephalin was not altered by fluoxetine, which has no affinity for these sites at concentrations as high as 1000 nM. In rats trained to discriminate morphine from saline, fluoxetine at doses of 5 or 10 mg/kg were recognized as saline. Increasing the fluoxetine dose to 20 mg/kg did not result in generalization to either saline or morphine. The dose response curve for morphine generalization was not significantly altered by fluoxetine doses of 5 or 10 mg/kg. Those rats treated with the combination of morphine and 20 mg/kg of fluoxetine did not exhibit saline or morphine appropriate responding. Fluoxetine potentiates the analgesic properties of morphine without enhancing its affinity for opioid receptors or its discriminative stimulus properties. 30 references, 2 figures, 2 tables.
- Research Organization:
- Eli Lilly and Co., Indianapolis, IN
- OSTI ID:
- 5484049
- Journal Information:
- Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 36:24; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Fourteen. beta. -(bromoacetamido)morphine irreversibly labels. mu. opioid receptors in rat brain membranes
Photoaffinity labeling of opioid receptor with morphine-7,8-oxide (morphine epoxide)
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALKALOIDS
AMINES
ANALGESICS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
INHIBITION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MORPHINE
NARCOTICS
NERVES
NERVOUS SYSTEM
NEUROREGULATORS
OPIUM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
RECEPTORS
REFLEXES
RODENTS
SEROTONIN
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
UPTAKE
VERTEBRATES