An in vivo dialysis and behavioural study of the release of 5-HT by p-chloroamphetamine in reserpine-treated rats.
1. Reserpine (2.5 mg kg-1 i.p.) decreased rat brain 5-hydroxytryptamine (5-HT) by 86% 24 h later but most components of the 5-HT-dependent behavioural syndrome induced by p-chloroamphetamine (PCA, 5 mg kg-1 i.p.) or 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 5 mg kg-1 i.p.) over 1 h after administration were unaffected. However, Straub tail was increased after giving PCA or 5-MeODMT and head weaving was decreased after giving 5-MeODMT. 2. Frontal cortex extracellular 5-HT concentrations of vehicle pretreated rats before injection of PCA, as calculated from dialysate 5-HT concentrations, were about 1/1000th of corresponding brain values. Extracellular 5-hydroxyindoleacetic acid (5-HIAA) and brain values were comparable with each other. Dialysate 5-HT increased after PCA with peak values at 20-40 min. 3. Reserpine pretreatment reduced dialysate 5-HT concentration before PCA was given but the net increase (AUC) over the 1 h after PCA did not differ significantly from that seen in animals pretreated with vehicle. Dialysate 5-HIAA values slowly decreased after PCA injection in both reserpine and vehicle pretreated groups. 4. The results suggest that PCA causes the 5-HT syndrome by releasing 5-HT from the neuronal cytoplasm but that physiological release of 5-HT occurs from vesicular stores.
Adell
A
A
Department of Neurochemistry, Institute of Neurology, London.
Sarna
G S
GS
Hutson
P H
PH
Curzon
G
G
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D003956:Dialysis; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D000662:Amphetamines; D002395:Catecholamines; D008732:Methoxydimethyltryptamines; D012701:Serotonin; D010133:p-Chloroamphetamine; D012110:Reserpine