Lithium differs from anticonvulsant mood stabilizers in prefrontal cortical and accumbal dopamine release: Role of 5-HT1A receptor agonism

Junji Ichikawa*, Jin Dai, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Anticonvulsant mood stabilizers, e.g., valproic acid and carbamazepine, and atypical antipsychotic drugs (APDs), e.g., clozapine, quetiapine, olanzapine, risperidone, and ziprasidone, have been reported to preferentially increase dopamine (DA) release in rat medial prefrontal cortex (mPFC), an effect partially or fully inhibited by WAY100635, a selective 5-HT1A antagonist. These atypical APDs have themselves been reported to be effective mood stabilizers, although the importance of increased cortical DA release to mood stabilization has not been established. The purpose of the present study was to determine whether zonisamide, another anticonvulsant mood stabilizer, as well as lithium, a mood stabilizer without anticonvulsant properties, also increases prefrontal cortical DA release and, if so, whether this release is also inhibited by 5-HT1A antagonism. As with valproic acid and carbamazepine, zonisamide (12.5 and 25 mg/kg) increased DA release in the mPFC, but not the NAC, an increase abolished by WAY100635 (0.2 mg/kg). However, lithium (100 and 250 mg/kg) decreased DA release in the NAC, an effect also attenuated by WAY100635 (0.2 mg/kg). Lithium itself had no effect in the mPFC but the combination of WAY100635 (0.2 mg/kg) and lithium (100 and 250 mg/kg) markedly increased DA release in the mPFC. Furthermore, M100907 (0.1 mg/kg), a selective 5-HT2A antagonist, abolished this increase in DA release in the mPFC. These results indicate that not all mood-stabilizing agents but only those, which have anticonvulsant mood-stabilizing properties, increase DA release in the cortex, and that the effect is dependent upon 5-HT1A receptor stimulation. However, the combination of lithium and 5-HT1A blockade may result in excessive 5-HT2A receptor stimulation, relative to 5-HT1A receptor stimulation, both of which can increase prefrontal cortical DA release.

Original languageEnglish (US)
Pages (from-to)182-190
Number of pages9
JournalBrain research
Volume1049
Issue number2
DOIs
StatePublished - Jul 12 2005

Keywords

  • 5-HT and 5-HT receptors
  • Dopamine release
  • Lithium
  • Medial prefrontal cortex
  • Mood stabilizer
  • Nucleus accumbens
  • Zonisamide

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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