Original Article

Neuropsychopharmacology (2005) 30, 43–51, advance online publication, 22 September 2004; doi:10.1038/sj.npp.1300567

Preclinical Research

Sulpiride in Combination with Fluvoxamine Increases in vivo Dopamine Release Selectively in Rat Prefrontal Cortex

Yukio Ago1, Shigeo Nakamura1, Akemichi Baba2 and Toshio Matsuda1

  1. 1Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
  2. 2Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

Correspondence: Dr T Matsuda, Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan. Fax: 81 6 6879 8159; E-mail: matsuda@phs.osaka-u.ac.jp

Received 1 March 2004; Revised 11 August 2004; Accepted 16 August 2004; Published online 22 September 2004.

Top

Abstract

Coadministration of atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) enhances the release of monoamines such as dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the prefrontal cortex. To clarify the role of DA-D2/3 receptors in the combination effect, we examined the effects of coadministration of the selective DA-D2/3 antagonist sulpiride and the SSRI fluvoxamine on amine neurotransmitter release in rat prefrontal cortex. Sulpiride (10 mg/kg, i.p.) and fluvoxamine (10 mg/kg, i.p.) alone did not affect extracellular DA levels, while their coadministration caused a significant increase in DA levels. Sulpiride alone did not affect extracellular levels of 5-HT and NE in the prefrontal cortex, while fluvoxamine alone caused a marked increase in 5-HT levels and a slight increase in NE levels. Sulpiride did not affect the fluvoxamine-induced increases in extracellular levels of 5-HT and NE. The DA-D2/3 antagonist haloperidol (0.1 mg/kg) in combination with fluvoxamine also caused a selective increase in extracellular DA levels in the cortex. Coadministration of sulpiride and fluvoxamine did not affect extracellular DA levels in the striatum. Combination of systemic sulpiride and local fluvoxamine did not increase the DA levels, but that of systemic fluvoxamine with local sulpiride increased. The combination effect in increasing prefrontal DA levels was antagonized systemically, but not locally, by the 5-HT1A antagonist WAY100635 at a low dose. These findings suggest that the combination of prefrontal DA-D2/3 receptor blockade and 5-HT1A receptor activation in regions other than the cortex plays an important role in sulpiride and fluvoxamine-induced increase in prefrontal DA release.

Keywords:

sulpiride, fluvoxamine, combination, dopamine (DA) release, prefrontal cortex

Extra navigation

.
ADVERTISEMENT