Effects of GABAB receptor ligands in animal tests of depression and anxiety.
Preclinical evidence strongly implicates GABA(B) receptors in the pathophysiology of several psychiatric disorders including anxiety and depression. In the present study, we investigated the effects of the selective GABA(B) receptor agonists baclofen and SKF 97541, the GABA(B) receptor positive allosteric modulator CGP7930 and the GABA(B) receptor antagonist SCH 50911 in the modified forced swimming test (FST) and in the elevated zero maze test (EZM), i.e. in animal models predictive of antidepressant and antianxiety activities, respectively. The classical antidepressant imipramine and the anxiolytic diazepam were employed as control drugs in the FST and in the EZM, respectively. In the FST, baclofen (0.25 mg/kg), SKF 97541 (0.01-0.05 mg/kg) or CGP 7930 (1-3 mg/kg) and SCH 50911 (1-3 mg/kg) showed antidepressant-like activity, significantly decreasing immobility time; these effects were not related to changes in locomotor activity. The antidepressant effects produced by the GABA(B) receptor ligands were compared with that of imipramine (30 mg/kg). In the EZM, CGP 7930 (1 mg/kg) and SCH 50911 (1-3 mg/kg) produced anxiolytic-like effects, significantly increasing time spent in the open areas of the maze; those effects were comparable with the effects of diazepam (1-2 mg/kg). Our results indicate that differential manipulation of GABA(B) receptors can modify behaviors relevant to depression and anxiety. The GABA(B) receptor positive allosteric modulator CGP 7930 and the antagonist SCH 50911 show both antidepressant and anxiolytic profile, while the GABA(B) receptor agonists (baclofen and SKF 97541) produce effects that are characteristic of antidepressant drugs.
Frankowska
Małgorzata
M
Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. frankow@if-pan.krakow.pl
Filip
Małgorzata
M
Przegaliński
Edmund
E
D000494:Allosteric Regulation; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D001418:Baclofen / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D018757:GABA Modulators / Q000494:pharmacology / Q000627:therapeutic use; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008024:Ligands; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D023421:Models, Animal; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000188:drug therapy / Q000523:psychology
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; C438607:2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D018757:GABA Modulators; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008024:Ligands; D009025:Morpholines; D009943:Organophosphorus Compounds; D010636:Phenols; C068457:3-aminopropyl(methyl)phosphinic acid; D001418:Baclofen