Effect of disulfiram administration on brain tryptophan, serotonin and peripheral tryptophan content.
The prophylactic deterrent effect of disulfiram (DS) has been attributed to its ability to exacerbate sympathetic function. Though there are reports to indicate that DS administration could as well affect the neurotransmitter metabolism, few reports implicate the possibility of central nervous system (CNS) mediated anticraving effect of the drug. The present study involving the oral administration of DS to rats for 45 days has clearly shown a significant increase in 5-HT (815.4 +/- 74.7 ng/g, P < 0.01) and 5-HIAA (506.1 +/- 86.3 ng/g, P < 0.02) contents in brain when compared to control rats. The observed increase in 5-HT and 5-HIAA content was found to correlate (zeta = 0.89) with the concomitant increase in brain tryptophan content (4.15 +/- 1.05 nmol/g, P < 0.001) following DS administration. Further, the study on peripheral tryptophan content has shown an increase in both total and free fraction (ultrafiltrate) of plasma, which in turn was found to have an inverse relationship (zeta = -0.94, P < 0.05) with the decrease in liver tryptophan content following DS administration. Thus the observed increase in brain 5-HT level is attributed to the ability of DS to mobilise peripheral tryptophan for 5-HT synthesis in CNS. As there are reports to imply the hyposerotonergic function as responsible for craving, the present findings, that DS could enhance the 5-HT metabolism in brain, may partially explain the CNS mediated anticraving effect of DS.
Nagendra
S N
SN
Department of Neurochemistry, Psychopharmacology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Shetty
K T
KT
Subhash
M N
MN
Udaya
H B
HB
Pradhan
N
N
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004221:Disulfiram / Q000008:administration & dosage / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D008995:Monoamine Oxidase; D004221:Disulfiram