Serotonin inhibits synaptic glutamate currents in rat nucleus accumbens neurons via presynaptic 5-HT1B receptors

Authors

  • Masatoshi Muramatsu,

    1. Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden
    2. Present address: Department of Neurosurgery, Mie Prefectural General Medical Center, Yokkaichi city, Mie, Japan
    Search for more papers by this author
  • Maria Danet S. Lapiz,

    1. Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden
    Search for more papers by this author
  • Eiichiro Tanaka,

    1. Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden
    2. Present address: Department of Physiology, Kurume University School of Medicine, Kurume-shi, Japan
    Search for more papers by this author
  • Johan Grenhoff

    1. Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden
    Search for more papers by this author

Correspondence: J. Grenhoff, as above. E-mail: Johan.Grenhoff@fyfa.ki.se

Abstract

Neurons in the nucleus accumbens septi in brain slices from adult male rats were studied with patch clamp recording in the whole-cell conformation. Cells filled with Lucifer Yellow were identified as medium spiny neurons. Electrical stimulation close to the recorded cell evoked excitatory and inhibitory synaptic currents. In the presence of picrotoxin or bicuculline, stimulation at a holding potential of −90 mV evoked an inward excitatory current that was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μm), identifying it as an excitatory postsynaptic current (EPSC) mediated by glutamate acting at AMPA/kainate receptors. Serotonin (5-hydroxytryptamine, 5-HT; 3–100 μm in the bath) decreased the EPSC in about 90% of the cells. The action of 5-HT was mimicked by N-(3-trifluoromethylphenyl)-piperazine HCl (TFMPP), but not by (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) or (±)-2,5-dimethoxy-4-iodoamphetamine HCl (DOI). The 5-HT effect was antagonized by pindolol or cyanopindolol, but not by spiperone, ketanserin or tropisetron. Taken together, these results indicate that 5-HT acts at 5-HT1B receptors. The effect of 5-HT was potentiated by cocaine (0.3–3 μm) or the selective serotonin reuptake inhibitor citalopram. Miniature synaptic currents recorded in the presence of tetrodotoxin were inhibited by CNQX, identifying them as spontaneous miniature EPSCs. 5-HT reduced the frequency of these miniature EPSCs without affecting their amplitude, which indicates a presynaptic site of action. This presynaptic inhibition by 5-HT might be involved in the behavioural effects of cocaine.

Ancillary