In vivo electrophysiological examination of 5-HT2 responses in 5-HT2C receptor mutant mice (original) (raw)

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.

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Authors and Affiliations

  1. Neurobiological Psychiatry Unit, McGill University, 1033 Pine Ave. W., Montréal, Canada H3A 1A1, , , , ,
    L.E. Rueter & P. Blier
  2. UCSF Department of Psychiatry, Langley Porter Psychiatric Institute, 401 Parnassus Ave., San Francisco, CA 94143-0984, USA, , , , ,
    L.H. Tecott

Authors

  1. L.E. Rueter
  2. L.H. Tecott
  3. P. Blier

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Rueter, L., Tecott, L. & Blier, P. In vivo electrophysiological examination of 5-HT2 responses in 5-HT2C receptor mutant mice.Naunyn-Schmied Arch Pharmacol 361, 484–491 (2000). https://doi.org/10.1007/s002109900181

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