A quantitative autoradiographic study of serotonin(1A) receptor regulation. Effect of 5,7-dihydroxytryptamine and antidepressant treatments

J. G. Hensler, G. B. Kovachich, A. Frazer

Resultado de la investigación: Articlerevisión exhaustiva

174 Citas (Scopus)


There have been few studies investigating the effect of treatments that alter serotonergic neurotransmission on the density of serotonin(1A) (5-hydroxytryptamine(1A) [5-HT(1A)]) receptors, even though lesioning serotonergic neurons has been reported to enhance certain responses thought to be due to activation of 5-HT(1A) receptors and repeated treatment of rats with different types of antidepressants can diminish 5-HT(1A)-mediated responses. Consequently, the binding of 3H-8-hydroxy-2-(di-n-propylamino)-tetralin (DPAT) to 5-HT(1A) receptors in serotonergic cell body and terminal field areas of rat brain was measured by quantitative autoradiography following either the lesioning of serotonergic neurons with 5,7 dihydroxytryptamine (5,7-DHT), or after chronic administration of monoamine oxidase inhibitors (MAOIs) (clorgyline, phenelzine, or tranylcypromine) or inhibitors of 5-HT uptake (citalopram or sertraline). Treatment of rats with 5,7-DHT did not cause any significant increase in binding of 3H-DPAT to 5-HT(1A) receptors in any area of the brain examined. There was no significant reduction in the binding of 3H-DPAT in terminal field areas of serotonergic innervation in rats treated with 5,7-DHT except in the CA2/CA3 region of the hippocampus (33% to 35% reduction). In the dorsal and median raphe nuclei, the specific binding of 3H-DPAT was reduced by treatment of rats with 5,7-DHT. In lesioned rats, the binding of 3H-cyanoimipramine (3H-CN-IMI) to uptake sites for serotonin was essentially eliminated in all terminal field areas examined, as well as in the dorsal and median raphe nuclei. Repeated administration of clorgyline, phenelzine, tranylcypromine, citalopram, or sertraline produced an attenuation of the hypothermic response of rats to acute subcutaneous injection of the 5-HT(1A)-receptor-agonist DPAT. In spite of this change in 5-HT(1A) responsivity, these treatments caused in the same animals no consistent change in the binding of 3H-DPAT in either serotonergic cell body or terminal field areas. Of the five drugs studied that diminished DPAT-induced hypothermia, only phenelzine and clorgyline significantly reduced the binding of 3H-DPAT, and even then in only a few of the 12 areas of brain measured. As a result of treatment of rats with tranylcypromine there was a significant increase in the binding of 3H-DPAT in the CA2/CA3 region of the hippocampus. We find, therefore, little evidence that the changes in the sensitivity of 5-HT(1A)-mediated behavioral and electrophysiologic responses following treatment with 5,7-DHT or chronic administration of antidepressant drugs are a result of changes in the density of 5-HT(1A) receptors as measured by the binding of 3H-DPAT in discrete areas of the brain of the rat.

Idioma originalEnglish (US)
Páginas (desde-hasta)131-144
Número de páginas14
EstadoPublished - 1991
Publicado de forma externa

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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