Modulation by fluoxetine of striatal dopamine release following Δ9-tetrahydrocannabinol: A microdialysis study in conscious rats

Daniel T. Malone, David A. Taylor

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Abstract

1. The present study was undertaken to investigate the effect of Δ9-tetrahydrocannabinol (Δ9-THC) and possible serotoninergic involvement on the extracellular level of dopamine (DA) in the striatum using microdialysis in conscious, freely-moving rats. 2. A dose-dependent increase in striatal DA release occurred after i.v. administration of 0.5-5 mg kg-1 Δ9-THC when compared with vehicle (n = 5-8, P < 0.05). Maximum increases, ranging from 42.1 ± 5.4% to 97.4 ± 5.9% (means ± s.e. mean) of basal levels occurred 20 min after Δ9-THC. This effect was abolished by pretreatment with the cannabinoid CB1 receptor antagonist, SR 141716 (2.5 mg kg-1 i.p.). 3. Pretreatment with fluoxetine (10 mg kg-1 i.p.) abolished the Δ9-THC-induced DA release. Fluoxetine 10 mg kg-1 i.p. administered 40 min after Δ9-THC had no significant effect on Δ9-THC-induced DA release. However, fluoxetine perfused locally into the striatum by adding it to the microdialysis perfusion fluid (10 μM) 40 min after Δ9-THC significantly potentiated the Δ9-THC-induced DA release (n = 6-8, P < 0.05). 4. These results suggest that DA release induced by Δ9-THC is modulated by serotoninergic changes induced by fluoxetine, the effect of which depends on the time of its administration relative to that of Δ9-THC. Fluoxetine induces an acute increase in extracellular 5-HT through reuptake inhibition, which can activate autoreceptors which may decrease serotoninergic neuronal activity. This may be the reason fluoxetine pretreatment abolished the Δ9-THC-induced DA release. The potentiation of Δ9-THC-induced DA release by fluoxetine perfusion added 40 min after Δ9-THC may be due to an acute increase in 5-HT produced by reuptake inhibition.

Original languageEnglish
Pages (from-to)21-26
Number of pages6
JournalBritish Journal of Pharmacology
Volume128
Issue number1
DOIs
Publication statusPublished - 20 Sep 1999

Keywords

  • Δ-THC
  • 5-HT
  • Dopamine
  • Fluoxetine
  • Microdialysis

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