Pharmacological characterisation of cortical gamma-aminobutyric acid type A (GABAA) receptors in two Wistar rat lines selectively bred for high and low anxiety-related behaviour.
Two Wistar rat lines that have been selectively bred for high-anxiety-related behaviour (HAB) and low-anxiety-related behaviour (LAB) in the elevated plusmaze test may be considered as a genetically prone animal model to study the neurochemical correlates of anxiety-related behaviour. Because there are pronounced differences between the two lines both in baseline levels of open-arm exploration in the elevated plus-maze test and in sensitivity to the anxiolytic effects of 1 mg/kg diazepam, we used these lines to investigate the pharmacology of the benzodiazepine binding site and the GABA binding site of cortical GABAA receptors. No difference in characteristics of flunitrazepam, zolpidem or muscimol binding to cortical GABAA receptors could be detected between the two lines. Although there was an increase in the brain concentration of the anxiolytic neuroactive steroid allopregnanolone, a potent positive allosteric modulator of GABAA receptors, both in HAB and LAB animals after a forced swim stress, allopregnanolone concentrations did not differ between the two lines. Moreover, plasma dehydroepiandrosterone (DHEA) concentrations were similar in HAB and LAB animals. We conclude that anxiety-related behaviour and benzodiazepine sensitivity in these rat lines are likely to be independent of the pharmacology of cortical GABAA receptors.
Hermann
B
B
Max Planck Institute of Psychiatry, Munich, Germany.
Landgraf
R
R
Keck
M E
ME
Wigger
A
A
Morrow
A L
AL
Ströhle
A
A
Holsboer
F
F
Rupprecht
R
R
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000378:metabolism*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018782:Maze Learning / Q000187:drug effects; D011280:Pregnanolone / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D012720:Severity of Illness Index; D013550:Swimming / Q000502:physiology
D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D003687:Dehydroepiandrosterone; D011280:Pregnanolone