ISSN:
1432-2072
Keywords:
5-HT uptake inhibition
;
Rats
;
Chronic treatment
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract In rats acute treatment with 5-HT uptake inhibitors antagonize p-chloro-amphetamine (PCA)-induced hypermotility and 5-HT depletion from brain. To compare the acute and chronic effect on neuronal 5-HT uptake these two effects of PCA were studied after 4 weeks feeding with diets containing the three 5-HT uptake inhibitors femoxetine, paroxetine, and chlorimipramine. Prolonged treatment with 5-HT uptake inhibitors reduce blood 5-HT due to blocked 5-HT uptake into platelets. Blood 5-HT and plasma concentrations of the 5-HT uptake inhibitors were determined. Femoxetine and paroxetine antagonized both effects of PCA and depleted blood 5-HT at plasma concentrations equivalent to those of patients treated with these substances. The results strongly indicate preservation of inhibited 5-HT uptake into neurons and platelets during prolonged treatment of rats with femoxetine and paroxetine. The plasma concentrations of chlorimipramine at the highest dose were lower than those of chlorimipramine treated patients, but the concentrations of desmethylchlorimipramine (DCIP) were higher. Inhibition of PCA-induced hypermotility and partial blood 5-HT depletion was obtained at these relatively low plasma levels of the substance itself, but the effect of PCA on brain 5-HT was not changed. In rats, it appears difficult under chronic conditions to keep the plasma concentrations of chlorimipramine high enough to inhibit neuronal 5-HT uptake without simultaneous high toxic concentrations of DCIP which is a weak 5-HT uptake inhibitor. The inhibition of PCA-hypermotility by chlorimipramine is probably caused by the dopamine receptor blockade of this substance.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00428108
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