Intrahippocampal infusion of the Ih blocker ZD7288 slows evoked theta rhythm and produces anxiolytic-like effects in the elevated plus maze

Authors

  • Michelle Yeung,

    1. Department of Psychology, University of Alberta, P-217 Biological, Sciences Building, Edmonton, Alberta, Canada T6G 2E9
    Search for more papers by this author
  • Clayton T Dickson,

    Corresponding author
    1. Department of Psychology, University of Alberta, P-217 Biological, Sciences Building, Edmonton, Alberta, Canada T6G 2E9
    2. Centre for Neuroscience, 5005-A Katz Group Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2E1
    3. Department of Physiology, 7-55 Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    • Department of Psychology, P-217 Biological Sciences Building, University of Alberta, Edmonton AB, Canada T6G 2E9
    Search for more papers by this author
  • Dallas Treit

    1. Department of Psychology, University of Alberta, P-217 Biological, Sciences Building, Edmonton, Alberta, Canada T6G 2E9
    2. Centre for Neuroscience, 5005-A Katz Group Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2E1
    Search for more papers by this author

Abstract

Hippocampal theta rhythm has been associated with a number of behavioral processes, including learning and memory, spatial behavior, sensorimotor integration and affective responses. Suppression of hippocampal theta frequency has been shown to be a reliable neurophysiological signature of anxiolytic drug action in tests using known anxiolytic drugs (i.e., correlational evidence), but only one study to date (Yeung et al. (2012) Neuropharmacology 62:155–160) has shown that a drug with no known effect on either hippocampal theta or anxiety can in fact separately suppress hippocampal theta and anxiety in behavioral tests (i.e., prima facie evidence). Here, we attempt a further critical test of the hippocampal theta model by performing intrahippocampal administrations of the Ih blocker ZD7288, which is known to disrupt theta frequency subthreshold oscillations and resonance at the membrane level but is not known to have anxiolytic action. Intrahippocampal microinfusions of ZD7288 at high (15 µg), but not low (1 µg) doses slowed brainstem-evoked hippocampal theta responses in the urethane anesthetized rat, and more importantly, promoted anxiolytic action in freely behaving rats in the elevated plus maze. Taken together with our previous demonstration, these data provide converging, prima facie evidence of the validity of the theta suppression model. © 2012 Wiley Periodicals, Inc.

Ancillary