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.