Participant of serotonin turnover rate in the brain on barbital withdrawal convulsion.
The correlation between the development of barbital (B)-withdrawal signs and alterations in the metabolism of brain 5-hydroxytryptamine (5-HT) was studied. Barbital (B)-dependent rats were prepared by the B-Admixed Food method (DAF method). The B-dependent rats were grouped according to the following 5 states: G-I, B-dependent state; G-II, B-withdrawn state; G-III, cross-administration of nitrazepam (NZP) following B-withdrawal; G-IV, cross-administration of chlorpromazine (CPZ) following B-withdrawal; and G-V, cross-administration of phenytoin following B-withdrawal. The controls were comprised of naive rats (G-VI) and naive rats dosed in the same manner as the dependent rats. The brain 5-HT synthesis rate and the brain 5-hydraxyindole acetic acid (5-HIAA) elimination were measured at 44 to 48 hr after B-withdrawal in all groups (when withdrawal convulsion was still persisting in the B-withdrawn rats of the G-II group). The brain 5-HT synthesis rate was elevated significantly (P less than 0.001) in the rats with persistent B-withdrawal convulsion (G-II) as compared with that in the B-dependent rats (G-I). Cross-administration of nitrazepam caused the elevation of 5-HT synthesis rate with B-withdrawal to be inhibited to the dependent level in parallel with the inhibition of B-withdrawal signs. On the other hand, CPZ and phenytoin, which inhibit B-withdrawal convulsion slightly, failed to recover completely the 5-HT turnover rate during B-withdrawal. From these results, it is obvious that the elevation of the brain 5-HT synthesis rate with B-withdrawal plays an important role in eliciting B-withdrawal convulsion.
D000818:Animals; D001462:Barbital / Q000009:adverse effects*; D001463:Barbiturates / Q000009:adverse effects*; D001921:Brain / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009567:Nitrazepam / Q000494:pharmacology / Q000627:therapeutic use; D010672:Phenytoin / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism*
D001463:Barbiturates; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D001462:Barbital; D010672:Phenytoin; D009567:Nitrazepam; D002746:Chlorpromazine