The effects of chronic treatment with amitriptyline and MDL 72394 on the control of 5-HT release in vivo.
The purpose of the experiments reported were to determine whether chronic treatment with either a monoamine oxidase (MAO) inhibitor or an uptake inhibitor would increase extracellular levels of 5-HT in vivo and whether such treatment resulted in a down-regulation of the 5-HT1B-mediated decrease in extracellular levels of 5-HT. Rats were given either saline, (E)-beta-fluoromethyline-m-tyrosine (MDL 72394 0.25 mg/kg p.o.) or amitriptyline (10 mg/kg p.o.) once a day for 21 days. Twenty-four hr after the final injection, dialysis loops were implanted into the frontal cortices of these rats and basal extracellular levels of 5-HT were measured. The effect of the 5-HT1 receptor agonist 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole succinate (RU 24969 10 mg/kg i.p.) on the extracellular level of 5-HT was then studied. Basal levels of 5-HT in saline-treated rats was found to be 27.9 +/- 3.9 fmol/20 microliters perfusate. Chronic treatment with amitriptyline had no effect on extracellular levels of 5-HT but chronic treatment with MDL 72394 significantly increased extracellular levels of 5-HT. Chronic treatment with either MDL 72394 or amitriptyline had no significant effect on the ability of RU 24969 to reduce extracellular levels of 5-HT. These results suggest that 5-HT1B receptors are not down-regulated in response to chronically raised extracellular levels of 5-HT.
Sleight
A J
AJ
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Smith
R J
RJ
Marsden
C A
CA
Palfreyman
M G
MG
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003956:Dialysis; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D000639:Amitriptyline; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D014443:Tyrosine; C046880:beta-fluoromethylene-3-tyrosine