The effect of ipsapirone and S(-)-pindolol on dopamine release in rat striatum and nucleus accumbens

Junji Ichikawa*, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Serotonin (5-hydroxytryptamine, 5-HT)(1A) receptor agonism and 5-HT(2A) receptor antagonism are components in the action of some of the recently developed antipsychotic drugs, e.g., clozapine and ziprasidone. However, studies of the role of 5-HT(1A) receptor agonism in the ability of these drugs to modulate dopamine (DA) release in the nucleus accumbens (NAC), which may be relevant to antipsychotic action, are lacking. Thus, we examined the effect of clinically available agents, ipsapirone, a 5-HT(1A) receptor partial agonist, and the mixed 5-HT(1A/1B)/β receptor antagonist S(-)- pindolol, on DA release in the NAC compared to the striatum (STR). Ipsapirone produced a biphasic effect; low dose (0.1 mg/kg) decreased, high dose (3 mg/kg) increased and intermediate doses (0.1 and 1 mg/kg) did not change DA release in the NAC, respectively. However, ipsapirone, at all doses (0.3, 1, 3, but not 0.1 mg/kg) increased striatal DA release. S(-)-pindolol (3, 10, but not 1 mg/kg) produced a comparable increase in DA release in the NAC and STR. These results suggest that the ability of lower dose of ipsapirone to decrease DA release in the NAC is more likely to be due to 5-HT(1A) receptor agonism. On the other hand, the effect of higher dose of ipsapirone on striatal DA release may be due to 5-HT(1A) receptor antagonism, as is the case with S(-)-pindolol. The mechanism and clinical significance of these results for developing antipsychotic drugs is discussed.

Original languageEnglish (US)
Pages (from-to)445-451
Number of pages7
JournalBrain Research
Volume842
Issue number2
DOIs
StatePublished - Sep 25 1999

Keywords

  • 5-HT(1A) receptor
  • Dopamine release
  • In vivo microdialysis
  • Ipsapirone
  • Nucleus accumbens and striatum
  • Rat
  • S(-)-pindolol

ASJC Scopus subject areas

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

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