Psychopharmacology

, Volume 149, Issue 3, pp 277–285

Distress vocalizations in maternally separated mouse pups: modulation via 5-HT1A, 5-HT1B and GABAA receptors

  • Eric W. Fish
  • Marzenka Sekinda
  • Pier F. Ferrari
  • Anneloes Dirks
  • Klaus A. Miczek
Original Investigation

DOI: 10.1007/s002130000370

Cite this article as:
Fish, E., Sekinda, M., Ferrari, P. et al. Psychopharmacology (2000) 149: 277. doi:10.1007/s002130000370

Abstract 

Rationale: Young rodents emit ultrasonic vocalizations (USVs) when separated from their dams and littermates. Pharmacological agents that act on GABAA and/or 5-HT receptors and that alleviate anxiety in humans reduce the emission of these calls. Objectives: 1) to investigate specific 5-HT1 receptor subtypes that modulate maternal separation-induced USVs in mice; 2) to assess the behavioral specificity of these effects; and 3) to compare 5-HT1 agonists with a positive neurosteroid modulator of the GABAA receptor complex. Methods: Seven-day old CFW mouse pups were isolated from their littermates and placed onto a 20°C surface for 4 min. USVs between 30 and 80 kHz, grid crossing, and rectal temperature were measured in separate groups of mouse pups following subcutaneous administration of 5-HT1A and 5-HT1B receptor agonists and antagonists, the neurosteroid allopregnanolone, or the benzodiazepine midazolam. Results: The 5-HT1A agonists (+)8-OH-DPAT (0.01–0.1 mg/kg) and flesinoxan (0.3–1.0 mg/kg), the selective 5-HT1B agonist CP-94,253 (0.03–30.0 mg/kg), and the mixed 5-HT1B/2C receptor agonist TFMPP (0.1–10.0 mg/kg) dose-dependently reduced USVs. These effects were reversed by the 5-HT1A receptor antagonist WAY 100,635 (0.1 mg/kg) or the 5-HT1B/D receptor antagonist GR 127935 (0.1 mg/kg). The effects of TFMPP were biphasic; low doses (i.e. 0.01 and 0.03 mg/kg) increased the rate of vocalization. Midazolam and allopregnanolone also reduced USVs. The highest doses of flesinoxan, (+)8-OH-DPAT, and allopregnanolone suppressed locomotion, whereas CP-94,253, TFMPP, and midazolam stimulated motor activity. Conclusions: These experiments confirm that agonists at the 5-HT1 receptors and a positive allosteric modulator of the GABAA receptor complex decrease maternal separation-induced USVs in mice, with 5-HT1B manipulations dissociating the effects on vocalizations from sedative effects.

Key words Anxiety Serotonin GABA Neurosteroid Ultrasonic vocalization Motor activity 

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Eric W. Fish
    • 1
  • Marzenka Sekinda
    • 1
  • Pier F. Ferrari
    • 2
  • Anneloes Dirks
    • 3
  • Klaus A. Miczek
    • 4
  1. 1.Department of Psychology, Tufts University, Medford, Massachusetts, USAUS
  2. 2.Institute of Human Physiology, University of Parma, Parma, ItalyIT
  3. 3.Department of Psychopharmacology, Utrecht University, Utrecht, The NetherlandsNL
  4. 4.Department of Psychiatry, Pharmacology and Experimental Therapeutics, and Neuroscience, Tufts University, Medford, Massachusetts, USAUS
  5. 5.Research Building, Tufts University, 490 Boston Avenue, Medford, MA 02155, USA e-mail: kmiczek@emerald.tufts.edu, Fax: +1-617-627-3939US

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