Dopaminergic input is required for increases in serotonin output produced by behavioral activation: an in vivo microdialysis study in rat forebrain

A. Mendlin, F. J. Martín, B. L. Jacobs

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Previous research has demonstrated that pharmacological stimulation of postsynaptic dopamine D2 receptors produces increases in serotonin output. The present study explored whether this relationship also holds under physiological conditions. Accordingly, we examined the effects of D2 receptor blockade or unilateral dopamine depletion on behaviorally induced increases in extracellular serotonin levels in the corpus striatum and prefrontal cortex of freely moving rats using in vivo microdialysis. Extracellular levels of dopamine and serotonin, as well as behavioral activity, were increased by both mild tail pinch and the light-dark transition. Tail pinch-induced increases in serotonin levels (39±3% and 53±5% in the corpus striatum and prefrontal cortex, respectively), but not the accompanying behavioral changes, were blocked by local application of the D2 receptor antagonist raclopride (10μM). D2 receptor blockade also disrupted the positive relationship between striatal serotonin levels and behavioral activity of animals across the light-dark transition (r=0.93 without raclopride, r=0.24 in presence of raclopride). Unilateral 6-hydroxydopamine lesion of the nigrostriatal dopaminergic system also abolished increases in striatal serotonin output induced by both tail pinch and light-dark transition. A negative correlation was observed between the degree of striatal dopamine depletion and tail pinch-induced increases in serotonin efflux (r=-0.88). Thus, both a local blockade of postsynaptic D2 receptors and striatal dopamine depletion prevented increases in serotonin output that normally accompany behavioral activation.These data indicate that the increases in the forebrain serotonin output produced by two distinct physiological/environmental manipulations appear to be largely dependent upon intact local dopaminergic neurotransmission. Copyright (C) 1999 IBRO.

Original languageEnglish (US)
Pages (from-to)897-905
Number of pages9
Issue number3
StatePublished - Aug 1999

All Science Journal Classification (ASJC) codes

  • General Neuroscience


  • 5-Hydroxytryptamine
  • 6-OHDA
  • Dopamine D receptors
  • Light-dark cycle
  • Microdialysis
  • Tail pinch


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