Blockade of potentiated startle responding in rats by 5-hydroxytryptamine1A receptor ligands.
A potentiated whole-body startle response was produced in rats by pairing intense acoustic stimuli with a light (conditional stimulus) formerly presented contiguously with electric shock. Administration of the selective serotonin (5-HT) 1A ligand 8-hydroxy-2-(di-n-propylamino)tetralin (0.125 and 0.5 mg/kg) blocked the potentiation of startle induced by the conditional stimulus. 1-[3-Chlorophenyl]piperazine, a non-anxiolytic 5-HT1B/1C agonist, did not block potentiated startle, even at a dose (1.0 mg/kg) that induced significant overall decreases in startle amplitude. The non-benzodiazepine anxiolytics buspirone (1.25-5.0 mg/kg), gepirone (3.0-10.0 mg/kg) and the related 5-HT1A ligand ipsapirone (1.0-10.0 mg/kg) blocked potentiated startle, though effects of the non-selective serotonin antagonist methysergide (0.3-10.0 mg/kg) fell short of significance. These data support a role for the 5-HT1A binding site in the anti-anxiety effects of buspirone and related compounds over a range of behavioral procedures.
Mansbach
R S
RS
Department of Psychiatry, University of California at San Diego, La Jolla 92093.
Geyer
M A
MA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D009281:Naphthalenes; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C039979:gepirone; C015068:1-(3-chlorophenyl)piperazine; D002065:Buspirone; D008784:Methysergide