Inhibition of 5,7-dihydroxytryptamine-induced supersensitivity to 5-hydroxytryptophan in mice by treatment with cycloheximide.
Intracisternal injection  of 5,7-dihydroxytryptamine (5,7-DHT) following treatment with desmethylimipramine induced development of behavioral supersensitivity to the intraperitoneally administered serotonin precursor 5-hydroxytryptophan (5-HTP) in the mouse. This behavioral syndrome, characterized by tremor and muscle twitches (myoclonus), showed a clear dose-response relationship with 5,7-DHT as well as with 5-HTP. Mice lesioned with a low dose of 5,7-DHT (20 micrograms) or a placebo were treated repeatedly with a protein synthesis inhibitor, sycloheximide (45 mg/kg, s.c., every 12 h for up to 10 days). This treatment resulted in a reversible decrease of cerebral protein synthesis varying between 70 and 20% with time between treatments. The myoclonic response to 5-HTP in animals pretreated with 5,7-DHT and by cycloheximide showed a decrease in intensity within 24 h when evaluated quantitatively by an electronic activity monitor, the results of which were confirmed by direct observation. Cycloheximide also exerted a similar, though smaller, effect following full development of sensitivity to 5-HTP over 10 days. These effects may de mediated by inhibition of rapidly turning over serotonin receptor proteins, although their interpretation is somewhat obscured by possible toxic effects of cycloheximide.
D015116:5,7-Dihydroxytryptamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004102:Dihydroxytryptamines / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009068:Movement / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009469:Neuromuscular Junction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011292:Premedication; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism
D004102:Dihydroxytryptamines; D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D003513:Cycloheximide; D006916:5-Hydroxytryptophan; D003891:Desipramine; D009638:Norepinephrine