Effects of amphetamine and chlordiazepoxide on probenecid-induced accumulation of acidic metabolites in the cerebrospinal fluid of the dog
Deluca, D.C.; Angel, C.; Murphree, O.D.
Biological Psychiatry 12(4): 577-582
1977
ISSN/ISBN: 0006-3223 PMID: 196692 Document Number: 113073
The view that various types of behavior are mediated or influenced by neurotransmitters led to investigation of the possibility that there might be strain-dependent differences in these dogs in the turnover rates of compounds associated with the neurotransmission process. Neff et al. (1967) suggested that measurement of the probenecid-induced accumulation of acidic metabolites in cerebrospinal fluid (CSF) might be used as an estimate of turnover rates of some neurotransmitters. This technique was applied in studies on dogs for 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), cyclicAMP and cGMP. This report attempts to correlate the neurochemical observations made by the application of the probenecid-induced accumulation of acid metabolite technique with the behavioral observations made with chlordiazepoxide and amphetamine. In evaluating the effect of amphetamine, there was a striking increase in CSF cAMP for both strains, but it was without effect on cGMP accumulation. Amphetamine, which stimulates catecholaminergic function, causes a striking increase in probenecid-induced accumulation of cAMP but is without effect on cGMP accumulation.