Modification of the anxiolytic action of 5-HT1A compounds by GABA-benzodiazepine agents in rats.
The general purpose of the present study was to analyze the possible interactions between the GABA benzodiazepine and the serotonin systems in the mediation of the antianxiety actions of 5-HT1A compounds. The anxiolytic effect of buspirone (5 mg/kg), ipsapirone (5 mg/kg), indorenate (5 mg/kg), and 8-OH-DPAT (0.5 mg/kg) was established in the rat burying behavior test. Flumazenil (5 mg/kg), but not bicuculline (2.5 mg/kg), effectively counteracted the reduction in burying behavior produced by buspirone, ipsapirone, and 8-OH-DPAT. These same 5-HT1A compounds, at subthreshold doses, produced an important reduction in burying behavior when combined with diazepam (0.25 mg/kg). The effect of indorenate was not altered by any of the antagonists and, when combined with diazepam it produced large increases in burying behavior latency. Only buspirone alone and in combination with bicuculline or flumazenil impaired motor coordination as tested in the rota rod. Data are discussed on the bases of the interaction between the GABAergic and serotonergic systems, stressing species differences and variations due to the animal model of anxiety.
Fernández-Guasti
A
A
Departamento de Farmacología y Toxicología, CINVESTAV, Instituto Mexicano de Psiquiatría, México DF.
López-Rubalcava
C
C
D008735:5-Methoxytryptamine / Q000008:administration & dosage / Q000031:analogs & derivatives; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D001640:Bicuculline / Q000008:administration & dosage; D002065:Buspirone / Q000008:administration & dosage; D003975:Diazepam / Q000008:administration & dosage; D004347:Drug Interactions; D005442:Flumazenil / Q000008:administration & dosage; D018755:GABA Agonists / Q000008:administration & dosage*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011743:Pyrimidines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1
D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D008735:5-Methoxytryptamine; D005442:Flumazenil; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C033600:indorenate; D003975:Diazepam; D002065:Buspirone; D001640:Bicuculline