Strychnine seizure potentiation by azaspirodecanedione anxiolytics in rats

• Published in: European journal of pharmacology Vol. 155; no. 3; p. 279
• Main Authors: Anderson, M C, Chung, E, Van Woert, M H
• Format: Journal Article
• Language: English
• Published: Netherlands 18-10-1988
• Subjects: Animals; Anti-Anxiety Agents - toxicity; Buspirone - toxicity; Drug Synergism; Male; Olivary Nucleus - drug effects; Pyridines - toxicity; Pyrimidines - toxicity; Rats; Rats, Inbred Strains; Receptors, Serotonin - drug effects; Seizures - chemically induced; Strychnine; Syndrome
• ISSN: 0014-2999
• DOI: 10.1016/0014-2999(88)90514-6

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.