Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 361, Issue 5, pp 484–491

In vivo electrophysiological examination of 5-HT2 responses in 5-HT2C receptor mutant mice

  • L.E. Rueter
  • L.H. Tecott
  • P. Blier
Original Article

Abstract.

The present study used 5-HT2C receptor mutant mice and their wild-type littermates to characterize the 5-HT2 receptor using the 5-HT2 agonists (±)-2-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and 1-(3-chlorophenyl)piperazine (mCPP) applied locally in the orbitofrontal cortex (OFC) and head of the caudate nucleus. Microiontophoretically-applied 5-HT, DOI and mCPP induced current-dependent inhibition of neuronal firing activity in both brain regions. There was no difference between 5-HT2C receptor mutants and wild-type mice in the ability of 5-HT or DOI to inhibit neuronal firing at any current used. In contrast, there was a reduced ability of mCPP to inhibit firing activity in the OFC when ejected at 10 nA. Unexpectedly, there was a small but significant increase in mCPP-induced inhibition in the caudate nucleus of mutant mice. In the OFC, the 5-HT2A antagonist MDL 100907 (2 mg/kg, i.p.) significantly antagonized the effect of both DOI and mCPP. In contrast, the non-selective 5-HT antagonist clozapine (10 mg/kg, i.p.) significantly antagonized only mCPP in the wild-type mice. However, neither MDL 100907 nor clozapine antagonized DOI or mCPP in the caudate nucleus. Finally, it required significantly less quisqualate to activate neurons in the 5-HT2C receptor mutants than in the wild-type mice, suggesting that 5-HT2C receptors serve a tonic inhibitory role in membrane excitability. The present results indicate that the inhibitory action of DOI is predominantly mediated by the 5-HT2A receptor in the OFC. mCPP, when applied locally, inhibits OFC firing activity by acting on both 5-HT2A and 5-HT2C receptors. However, DOI and mCPP might be acting in the caudate nucleus through an atypical 5-HT2 receptor yet to be characterized.

Orbitofrontal cortex Caudate nucleus DOI mCPP MDL 100907 Clozapine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • L.E. Rueter
    • 1
  • L.H. Tecott
    • 2
  • P. Blier
    • 1
  1. 1.Neurobiological Psychiatry Unit, McGill University, 1033 Pine Ave. W., Montréal, Canada H3A 1A1
  2. 2.UCSF Department of Psychiatry, Langley Porter Psychiatric Institute, 401 Parnassus Ave., San Francisco, CA 94143-0984, USA
  3. 3.Present address: Abbott Laboratories, AP9A, 47W, 100 Abbott Park Rd., Abbott Park, IL 60064-6115, USA

Personalised recommendations