Behavioral effects of agents active at the gamma-aminobutyric acid receptor complex in the staircase paradigm.
This study examined the behavioral effects of agents active at the gamma-aminobutyric acid (GABA(A)) receptor complex in the mouse staircase paradigm. The neuroactivesteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were compared with the benzodiazepine agonist clonazepam, the non-benzodiazepine hypnotic compound zopiclone, and the antiepileptic agent gabapentin. Clonazepam, zopiclone and gabapentin reduced rearing activity at doses that did not affect climbing. The rearing-suppression effect of clonazepam and zopiclone, but not of gabapentin, was blocked by the benzodiazepine antagonist flumazenil, suggesting that the added effect of gabapentin is not mediated by the benzodiazepine receptor on the GABA complex. DHEA suppressed rearing behavior at doses that did not reduce climbing, but analysis with the Bonferroni post hoc test yielded no statistically significant difference. This inhibitory effect was attenuated by flumazenil. By contrast, DHEA-S suppressed, in a dose-dependent manner, both rearing and climbing behavior to the same extent. The findings support the potential value of the mouse staircase paradigm for demonstrating behaviorally relevant anxiolysis of test compounds shown to interact in vitro with the GABA(A) receptor complex.
Weizman
R
R
Tel Aviv Community Mental Health Center, Tel Aviv, Israel.
Paz
L
L
Peter
Y
Y
Toren
P
P
Pick
C G
CG
D000085:Acetates; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000588:Amines; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D053961:Azabicyclo Compounds; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002998:Clonazepam / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D000077206:Gabapentin; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D000276:Adjuvants, Immunologic; D000588:Amines; D014151:Anti-Anxiety Agents; D053961:Azabicyclo Compounds; D003509:Cyclohexanecarboxylic Acids; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011963:Receptors, GABA-A; C515050:zopiclone; D005442:Flumazenil; D003687:Dehydroepiandrosterone; D005680:gamma-Aminobutyric Acid; D019314:Dehydroepiandrosterone Sulfate; D002998:Clonazepam; D000077206:Gabapentin