PROBENECID-INDUCED ACCUMULATION OF CYCLIC NUCLEOTIDES, 5-HYDROXYINDOLEACETIC ACID, AND HOMOVANILLIC-ACID IN CISTERNAL SPINAL-FLUID OF GENETICALLY NERVOUS DOGS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 11  (6) , 743-753
Abstract
Forty dogs, 20 each of a genetically nervous strain and of a normal strain of short-haired pointers were studied. The nervous strain after about age 3 mo. displayed extreme hypervigilance, timidity, human avoidance and often showed catatonic-like muscle rigidity when in the presence of humans or novel stimuli. Measurements of probenecid-induced accumulation of acid metabolites in cisternal CSF were carried out. Among the compounds measured at 1.5-6.0 h after probenecid treatment, homovanillic acid was similar for the 2 strains, 5-hydroxyindoleacetic acid was lower but c[cyclic]AMP and cGMP were higher for the nervous strain compared with age- and sex-matched behaviorally normal dogs. Probenecid levels in CSF were similar at all points in time from 1.5-6.0 h after its i.v. administration in a dose of 50 mg/kg body weight. Previously observed differences in the 2 strains are supported and suggest that hyperresponsiveness of the CNS noradrenergic and cholinergic systems and a hyporesponsiveness of the serotoninergic system are related to the genetically expressed aberrant behavior.