Psychopharmacology

, Volume 190, Issue 4, pp 541–553

Behavioral evaluation of mice deficient in GABAB(1) receptor isoforms in tests of unconditioned anxiety

Authors

  • Laura H. Jacobson
    • Novartis Institutes for BioMedical ResearchNovartis Pharma AG
  • Bernhard Bettler
    • Department of Clinical-Biological Sciences, Pharmazentrum, Institute of PhysiologyUniversity of Basel
  • Klemens Kaupmann
    • Novartis Institutes for BioMedical ResearchNovartis Pharma AG
    • Novartis Institutes for BioMedical ResearchNovartis Pharma AG
    • Department of Pharmacology and Therapeutics, School of PharmacyUniversity College Cork
Original Investigation

DOI: 10.1007/s00213-006-0631-9

Cite this article as:
Jacobson, L.H., Bettler, B., Kaupmann, K. et al. Psychopharmacology (2007) 190: 541. doi:10.1007/s00213-006-0631-9

Abstract

Rationale

Emerging data support a role for GABAB receptors in anxiety. GABAB receptors are comprised of a heterodimeric complex of GABAB1 and GABAB2 receptor subunits. The predominant neuronal GABAB1 receptor isoforms are GABAB(1a) and GABAB(1b). Recent findings indicate specific roles for these isoforms in conditioned fear responses, although their influence on behavior in tests of unconditioned anxiety is unknown.

Objective

The aim of this study was to examine the role of the GABAB(1) isoforms in unconditioned anxiety.

Materials and methods

Mice deficient in the GABAB(1a) or GABAB(1b) receptor isoforms were examined in a battery of anxiety tests.

Results

In most tests, genotype did not significantly affect anxious behavior, including the elevated plus maze, marble burying, and stress-induced hypothermia tests. Corticosterone and adrenocorticotropic hormone levels were similarly unaffected by genotype. Female, but not male, \( {\text{GABA}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }}_{{{\text{B}}{\left( {1{\text{a}}} \right)}}} \) and \( {\text{GABA}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }}_{{{\text{B}}{\left( {1{\text{b}}} \right)}}} \) mice showed increased anxiety relative to wild-type controls in the elevated zero maze. In the staircase test, male \( {\text{GABA}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }}_{{{\text{B}}{\left( {1{\text{b}}} \right)}}} \) mice defecated more than male \( {\text{GABA}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }}_{{{\text{B}}{\left( {1{\text{a}}} \right)}}} \) mice, although no other test parameter was influenced by genotype. In the light–dark box, female \( {\text{GABA}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }}_{{{\text{B}}{\left( {1{\text{a}}} \right)}}} \) mice spent less time in the light compartment compared to the \( {\text{GABA}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }}_{{{\text{B}}{\left( {1{\text{b}}} \right)}}} \) females, whereas male \( {\text{GABA}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }}_{{{\text{B}}{\left( {1{\text{b}}} \right)}}} \) mice made fewer light–dark transitions than \( {\text{GABA}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-\nulldelimiterspace} - }}_{{{\text{B}}{\left( {1{\text{a}}} \right)}}} \) males.

Conclusions

Specific roles for either GABAB(1) isoform in unconditioned anxiety were not explicit. This differs from their contribution in conditioned anxiety and from the anxious phenotype of GABAB1 and GABAB2 subunit knockout mice. The findings suggest that the GABAB(1) isoforms have specific relevance for anxiety with a cognitive component, rather than for innate anxiety per se.

Keywords

AnxietyUnconditionedPoint mutationGABAB(1) receptor isoformsTest battery

Copyright information

© Springer-Verlag 2006