Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze.
The effects of several 5-HT1A agonists and excitatory amino acid antagonists were compared to the standard benzodiazepines, diazepam and chlordiazepoxide (CDP) in two assays predictive of anxiolytic activity, the social interaction and elevated plus maze procedures. Indicative of anxiolytic effects the 5-HT1A agonists, buspirone, gepirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all significantly increased social interaction time and open arm exploration time in the social interaction and elevated plus maze procedures, respectively. Likewise, anxiolytic activity in these assays were also produced by the competitive N-methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovaleric acid (AP-5), 2-amino-7-phosphonoheptanoic acid (AP-7), 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the non-competitive NMDA antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) while NMDA produced anxiogenic effects. Furthermore, the anxiolytic effects of these agents were of equal magnitude to the benzodiazepines. These two classes of compounds were differentiated in the yohimbine-induced seizure assay, with the NMDA antagonists dose dependently antagonizing seizures similar to the benzodiazepines while the 5-HT1A agonists were inactive. These results suggest that the 5-HT1A agonists and the NMDA antagonists may be potential non-classical anxiolytic agents with different mechanisms of action.
Dunn
R W
RW
Department of Biological Research, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ 08876.
Corbett
R
R
Fielding
S
S
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D011985:Receptors, Serotonin / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D012919:Social Behavior; D015016:Yohimbine / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D015016:Yohimbine