Effect of restraint stress and anxiolytics on 5-HT turnover in rat brain.
In male Tuck AHA rats, restraint stress had no effect on 5-hydroxytryptamine (5-HT) levels in the frontal cortex, amygdala, hypothalamus and hippocampus, but produced a significant increase in 5-hydroxyindoleacetic acid (5-HIAA) levels in the amygdala after 120 and 180 min, and in the hypothalamus after 180 min. This apparent increase in turnover was not paralleled by a concomitant increase in the rate of 5-HT synthesis, as determined by measuring the accumulation of 5-hydroxytryptophan (5-HTP) following inhibition of amino acid decarboxylase with m-hydroxybenzylhydrazine (NSD-1015). 5-HTP accumulation was, however, increased in the frontal cortex after 180 min. In naive rats, buspirone (0.1-2.5 mg/kg, s.c.) produced a dose-dependent decrease in 5-HTP accumulation in all four brain regions, while chlordiazepoxide, in doses up to 10 mg/kg (s.c.) had no effect. The increase in 5-HT synthesis in the frontal cortex following 180 min restraint stress was inhibited by pretreatment with buspirone, when administered at 2.5 mg/kg (s.c.) 30 min prior to the stress period, but not by chlordiazepoxide at 10 mg/kg (s.c.).
Mitchell
S N
SN
Department of Pharmacology, King's College (Chelsea Annexe), London, UK.
Thomas
P J
PJ
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002065:Buspirone / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors
D014151:Anti-Anxiety Agents; D006834:Hydrazines; D012701:Serotonin; D002707:Chlordiazepoxide; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D002065:Buspirone