5-HT4 receptors exert a frequency-related facilitatory control on dorsal raphé nucleus 5-HT neuronal activity

Authors

  • Guillaume Lucas,

    1. McGill University, Department of Psychiatry, Research and Training Building, Room 207, 1033 Avenue des Pins Ouest, Montréal, Québec, Canada H3A 1A1
    Search for more papers by this author
  • Guy Debonnel

    1. McGill University, Department of Psychiatry, Research and Training Building, Room 207, 1033 Avenue des Pins Ouest, Montréal, Québec, Canada H3A 1A1
    Search for more papers by this author

: Dr Debonnel, as above.
E-mail: guy.debonnel@mcgill.ca

Abstract

We investigated, using single-unit recordings in chloral hydrate-anaesthetized rats, the role of serotonin4 (5-HT4) receptors in the control of dorsal raphé nucleus (DRN) 5-HT neuron activity. About one-half (36) of the 76 neurons recorded were affected by either the preferential 5-HT4 agonist cisapride (500 and 1000 µg/kg, i.v.) or the selective 5-HT4 antagonist, GR 125487 (200– 2000 µg/kg, i.v.). Responding neurons displayed a significantly higher mean basal firing rate (1.93 ± 0.1 Hz) than non-responders (1.31 ± 0.1 Hz). The firing rate of responding 5-HT neurons was enhanced dose-dependently by cisapride (+47 and +94% at 500 and 1000 µg/kg, respectively), an effect abolished by GR 125487 (500 µg/kg) and reduced by the 5-HT4 antagonist, SDZ 205557 (500 µg/kg, i.v). Conversely, GR 125487 induced a dose-dependent inhibition of responders activity, which was almost completely suppressed at the dose of 2000 µg/kg. In a separate set of experiments, the selective 5-HT4 agonist, prucalopride (500 µg/kg, i.v), increased the firing activity (+35%) of 5-HT neurons displaying a high basal firing rate; subsequent injection of GR 125487 (500 µg/kg, i.v.) suppressed this effect. These results indicate that 5-HT4 receptors exert both a tonic and a phasic, positive, frequency-related control on DRN 5-HT neuronal activity. The existence of such a control might open new avenues for therapeutic research in the antidepressant field.

Ancillary