Increased extracellular serotonin in rat brain after systemic or intraraphe administration of morphine.
The effect of morphine on serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the CNS of unanesthetized rats was investigated by microdialysis. Morphine was administered either subcutaneously, by local perfusion into the diencephalon, or by intraraphe microinjection. Systemic administration of morphine resulted in a significant increase in both extracellular 5-HT and 5-HIAA in the diencephalon. The effect of morphine on 5-HT was dose dependent during local perfusion of the diencephalon with inhibitors of uptake or monoamine oxidase. Systemic morphine also produced significant increases in extracellular 5-HT in the striatum and hippocampus during uptake inhibition. The site of opioid effects on 5-HT was tested by locally perfusing morphine into the diencephalon. This had no effect on 5-HT or 5-HIAA. In contrast, intraraphe injection of morphine caused a dose-dependent increase in extracellular 5-HT and 5-HIAA in the diencephalon. These results suggest that systemic morphine induces an increase in 5-HT release in widespread areas of the forebrain. This appears to be due to an effect on 5-HT cell bodies and not on 5-HT nerve endings in projection sites.
Tao
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R
Department of Biological Sciences, Rutgers University, Piscataway, New Jersey 08855.
Auerbach
S B
SB
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D004027:Diencephalon / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007263:Infusions, Parenteral; D007279:Injections, Subcutaneous; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013238:Stereotaxic Techniques; D013997:Time Factors
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009020:Morphine