Fluoxetine, a selective inhibitor of serotonin uptake, potentiates morphine analgesia without altering its discriminative stimulus properties or affinity for opioid receptors

Journal Article · Mon Jun 17 00:00:00 EDT 1985 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(85)90321-2· OSTI ID:5484049

Hynes, M D; Lochner, M A; Bemis, K G; Hymson, D L

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), Vol. 36:24
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
NARCOTICS
RECEPTORS
SEROTONIN
INHIBITION
UPTAKE
AFFINITY
DOSE-RESPONSE RELATIONSHIPS
MORPHINE
NERVES
RATS
REFLEXES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALOIDS
AMINES
ANALGESICS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
OPIUM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RODENTS
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques