Differential effects of WAY-100135 on the decrease in 5-hydroxytryptamine release induced by buspirone and NAN-190.
1-(2-Methoxyphenyl)-4-[(phthalimido)butyl] piperazine (NAN-190) and 8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5] decane-7,9-dione (buspirone) are 5-HT1A receptor partial agonists which decrease 5-hydroxytryptamine (5-HT) release in vivo. In order to assess whether these ligands decrease 5-HT release by stimulating 5-HT1A receptors we examined the ability of the selective 5-HT1A receptor antagonist N-tert-butyl 3-4-(2-methoxyphenyl) piperazin-1-yl-2-phenylpropanamide dihydrochloride (WAY-100135) to block their inhibitory effects on 5-HT. NAN-190 (0.1 mg/kg s.c.) and buspirone (1.0 mg/kg s.c.) significantly decreased extracellular levels of 5-HT in hippocampal dialysates. WAY-100135 (10.0 mg/kg s.c.) attenuated the effect of buspirone but had no significant effect on the NAN-190-induced decreased in 5-HT release. These data demonstrate that buspirone is an agonist at the somatodendritic 5-HT1A receptor but that the inhibitory effects of NAN-190 on 5-HT release may be mediated via a mechanism other than, or in addition to, 5-HT1A receptor agonism.
Routledge
C
C
Department of Neuropharmacology, Wyeth Research, Maidenhead, Berkshire, UK.
Gurling
J
J
Ashworth-Preece
M A
MA
Dourish
C T
CT
D000818:Animals; D002065:Buspirone / Q000494:pharmacology*; D004347:Drug Interactions; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013238:Stereotaxic Techniques
D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C081293:WAY 100135; D012701:Serotonin; D002065:Buspirone