Strychnine seizure potentiation by azaspirodecanedione anxiolytics in rats.
Buspirone, gepirone and ipsaperone administered intraperitoneally (40 mg/kg) to naive rats were found to be proconvulsive for strychnine-induced seizures. The dose of strychnine required to induce seizures in 50% of test animals (CD50) was 2.18 mg/kg in naive rats, while CD50s for rats treated with the azaspirodecanediones ipsaperone, gepirone and buspirone were 1.65, 0.97 and 0.70 mg/kg respectively. Azaspirodecanediones have high affinity for the 5-HT1A serotonin receptor, however, the specific 5-HT1A agonist, 8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT) had no effect on strychnine seizure in naive rats (CD50 = 2.0 mg/kg). The strychnine specific proconvulsive effects of inferior olive lesions and buspirone were additive, resulting in a CD50 of 0.1 mg/kg. This observation indicates that the buspirone-induced decrease in strychnine seizure threshold does not require intact inferior olive-climbing fiber pathways. Cerebellar sites for possible azaspirodecanedione action are discussed.
Anderson
M C
MC
Department of Neurology, Mt. Sinai School of Medicine, New York, NY 10029.
Chung
E
E
Van Woert
M H
MH
D000818:Animals; D014151:Anti-Anxiety Agents / Q000633:toxicity*; D002065:Buspirone / Q000633:toxicity; D004357:Drug Synergism; D008297:Male; D009847:Olivary Nucleus / Q000187:drug effects; D011725:Pyridines / Q000633:toxicity; D011743:Pyrimidines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*; D013331:Strychnine; D013577:Syndrome
D014151:Anti-Anxiety Agents; D011725:Pyridines; D011743:Pyrimidines; D011985:Receptors, Serotonin; C010835:3-acetylpyridine; C043077:ipsapirone; D013331:Strychnine; C039979:gepirone; D002065:Buspirone