Anxiolytic-like effect of group III mGlu receptor antagonist is serotonin-dependent.
Literature data have provided evidence that antagonists of group I metabotropic glutamate receptors (mGluRs) and agonists of group II/III mGluRs show anxiolytic-like properties in preclinical studies. However data reporting anxiolytic-like action of group III mGlu receptor antagonists were also published. In the present paper we investigated the anxiolytic-like activity of the group III mGlu receptor antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG). To examine its anxiolytic-like effects, the basolateral amygdala was chosen as an injection site, as this brain region is involved in the regulation of anxiety-related behavior. To detect anxiolytic-like activity, the Vogel conflict-drinking test in rats was used. Intra-amygdalar injections of CPPG exhibited dose-dependent, potent anxiolytic-like action at a dose of 75 nmol, which was blocked by a concomitant administration of the group III mGlu receptor agonist CI (S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-I) at a dose of 7.5 nmol. The benzodiazepine receptor antagonist flumazenil (given intraperitoneally, 10 mg/kg) did not change the anxiolytic-like effect of CPPG, but that effect was abolished by the non-selective antagonist of 5-HT receptors metergoline and the antagonist of 5-HT2A/C receptors ritanserin (both given intraperitoneally at doses of 2 and 0.5 mg/kg, respectively). These findings suggest that the blockade of group III mGlu receptors in the amygdala is responsible for anxiolysis and that serotonergic, but not the benzodiazepine recognition site of the GABA-ergic system are involved in the anxiolytic-like response induced by group III mGlu antagonist.
Stachowicz
K
K
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
Chojnacka-Wójcik
E
E
Kłak
K
K
Pilc
A
A
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D003220:Conflict, Psychological; D003517:Cyclopentanes / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D004347:Drug Interactions; D004558:Electric Stimulation / Q000009:adverse effects; D005442:Flumazenil / Q000008:administration & dosage; D018757:GABA Modulators / Q000008:administration & dosage; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology; D016713:Ritanserin / Q000008:administration & dosage; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage; D014233:Tricarboxylic Acids / Q000627:therapeutic use
C409063:1-aminocyclopentane-1,2,4-tricarboxylic acid; D014151:Anti-Anxiety Agents; D003517:Cyclopentanes; D018757:GABA Modulators; D018094:Receptors, Metabotropic Glutamate; D012702:Serotonin Antagonists; D014233:Tricarboxylic Acids; C104331:cyclopropyl-4-phosphonophenylglycine; C102718:metabotropic glutamate receptor 3; D016713:Ritanserin; D012701:Serotonin; D005442:Flumazenil; D005998:Glycine