Combined lithium and valproate treatment and subsequent withdrawal: serotonergic mechanism of their interaction in discrete brain regions.
Rats were administered with lithium carbonate (1 mmole/kg), valproate (300 mg/kg) and their combination for 12 days. Rats in the withdrawal group were treated for 10 days, followed by saline for 2 days. Mid-brain tryptophan levels increased in all the groups except lithium-treated rats. The administration of lithium together with valproate decreased tryptophan hydroxylase activity and 5-hydroxytryptamine levels in certain brain regions compared to either treatment alone. Also, the magnitude of valproate-induced 5-hydroxyindoleacetic acid elevation was decreased after combined treatment. Most of the changes observed after combined exposure persisted even after 2 days of treatment withdrawal. It appears from the data that combined administration of the two drugs produces persistent decrease in 5-hydroxytryptamine synthesis and turnover in the brain.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D008094:Lithium / Q000009:adverse effects / Q000494:pharmacology*; D016651:Lithium Carbonate; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014635:Valproic Acid / Q000009:adverse effects / Q000494:pharmacology*
D016651:Lithium Carbonate; D012701:Serotonin; D014635:Valproic Acid; D008094:Lithium