Effects of GABAB receptor ligands in rodent tests of anxiety-like behavior.
GABAergic hypothesis of anxiety was introduced many years ago, however, a limited number of supporting data were accumulated so far and the role of GABA(B) receptors in behavioral processes related to the anxiety disorders has not been resolved. In the present study, we examined anxiolytic activity of CGP 36742, a potent and selective GABA(B) receptor antagonist, in rodent tests/models. We have demonstrated that CGP 36742 (30 mg/kg) is active in several animal tests detecting anxiolytic activity (the elevated plus-maze, conflict drinking test and four-plate test). Moreover, we examined the effects of another antagonist--CGP51176 and agonist--CGP 44532 of GABA(B) receptor in the four-plate test in mice. CGP 51176 (5 or 8 mg/kg) was inactive, while CGP 44532 (0.125 mg/kg) exhibited anxiogenic-like effect. These preclinical data further implicate GABA(B) receptor function in anxiety, and support the GABAergic hypothesis of this disorder.
Partyka
Anna
A
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Kłodzińska
Aleksandra
A
Szewczyk
Bernadeta
B
Wierońska
Joanna M
JM
Chojnacka-Wójcik
Ewa
E
Librowski
Tadeusz
T
Filipek
Barbara
B
Nowak
Gabriel
G
Pilc
Andrzej
A
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004597:Electroshock; D005106:Exploratory Behavior / Q000187:drug effects; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008024:Ligands; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010721:Phosphinic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000378:metabolism
C112036:3-amino-2-(S)-hydroxypropyl-methyl-phosphinic acid; C516672:3-amino-2-hydroxypropylcyclohexylmethylphosphinic acid; D014151:Anti-Anxiety Agents; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008024:Ligands; D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; C079148:(3-aminopropyl)(n-butyl)phosphinic acid; D005680:gamma-Aminobutyric Acid