Involvement of benzodiazepine binding sites in an antiaggressive effect by 5-HT(1A) receptor activation in isolated mice.
The effect of the benzodiazepine receptor antagonist flumazenil was examined on an antiaggressive effect of (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3- benzodioxole HCl (MKC-242), a 5-HT(1A) receptor agonist. MKC-242 (0.1-1.0 mg/kg, p.o.) selectively reduced isolation-induced aggressive behavior in a dose-dependent manner. Flumazenil (10 mg/kg, i.p.) antagonized the antiaggressive effects of MKC-242 and diazepam, although it alone did not affect the behaviors of isolated mice. These findings suggest that a gamma-aminobutyric acid(A) (GABA(A)) receptor system is involved in the antiaggressive effect by 5-HT(1A) receptor activation.
Sakaue
M
M
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Osaka 565-0871, Suita, Japan.
Ago
Y
Y
Murakami
C
C
Sowa
C
C
Sakamoto
Y
Y
Koyama
Y
Y
Baba
A
A
Matsuda
T
T
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D003975:Diazepam / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012934:Social Isolation
D004146:Dioxanes; D004149:Dioxoles; D018757:GABA Modulators; D010879:Piperazines; D011725:Pyridines; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D005442:Flumazenil; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C096294:osemozotan; D003975:Diazepam