Differential effects of 5,7-dihydroxytryptamine-induced serotoninergic degeneration of 5-HT1A receptors and 5-HT uptake sites in the rat brain.
The time-course of 5,7-dihydroxytryptamine-induced lesions (2, 5 and 14 days after i.c.v. injection of 150 micrograms) and the effects of acute reserpine treatment (10 mg/kg, i.p., one or 5 days before scheduled death), were evaluated by autoradiography of [3H]paroxetine binding sites in the rat brain. Reserpine had no significant effect on [3H]paroxetine binding, indicating that the depletion of serotonin is not sufficient per se to alter the serotonin uptake sites in any region. Two days after the 5,7-dihydroxytryptamine lesion, [3H]paroxetine binding was already decreased in the majority of brain regions. In the caudate putamen these binding sites were significantly decreased only 14 days after the lesion, whereas the ventral tegmental area (or the enclosed median forebrain bundle), the dorsal raphe (mainly the ventral portion) and the median raphe maintained their high density of serotonin uptake sites even after 14 days. Results were similar using [3H]citalopram as ligand for the serotonin uptake sites, in the brains of rats lesioned 5 days before death; an exception was the ventral portion of the dorsal raphe, where there was a significant increase with [3H]paroxetine and a decrease with [3H]citalopram binding. In adjacent sections of the same brains we also measured [3H]8-OH-DPAT binding, confirming that it completely disappears in the dorsal raphe after the lesion. Thus, considering the extent of serotonin cell body degeneration, there appears to be a paradoxical mismatch between the excessive loss of [3H]8-OH-DPAT binding and the resistance of [3H]citalopram or [3H]paroxetine binding in the dorsal raphe, suggesting that the two binding sites may undergo adaptive regulation in surviving neurons.
Gobbi
M
M
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Regondi
M C
MC
Pompeiano
M
M
Palacios
J M
JM
Mennini
T
T
D015116:5,7-Dihydroxytryptamine / Q000378:metabolism / Q000494:pharmacology*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D017374:Paroxetine / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*
D011985:Receptors, Serotonin; D015283:Citalopram; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017374:Paroxetine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine