| Autor: |
Bouali S; INSERM U288, NeuroPsychoPharmacologie Moléculaire Cellulaire et Fonctionalle, France. sbouali@ext.jussieu.fr, Evrard A, Chastanet M, Lesch KP, Hamon M, Adrien J |
| Jazyk: |
angličtina |
| Zdroj: |
The European journal of neuroscience [Eur J Neurosci] 2003 Oct; Vol. 18 (8), pp. 2203-12. |
| DOI: |
10.1046/j.1460-9568.2003.02960.x |
| Abstrakt: |
The serotonin transporter (5-HTT) is the target of most antidepressant drugs, whose therapeutic action is related to their facilitatory influence on 5-HT neurotransmission. In this study, we investigated the functional adaptive properties of 5-HT1A autoreceptors, which regulate serotonergic neuronal firing, in knockout mice deficient in 5-HTT. Neurons of the dorsal raphe nucleus (DRN) were recorded extracellularly under chloral hydrate anaesthesia in male and female knockout 5-HTT mice and their wild-type counterparts. The inhibitory response of DRN neurons to intravenous injection of the 5-HT1A agonist 8-OH-DPAT was dramatically reduced in knockout 5-HTT compared with wild-type mice, especially in females. Changes in 8-OH-DPAT-induced hypothermia and autoradiographic labelling of 5-HT1A sites in the DRN confirmed a greater level of desensitization/down-regulation of 5-HT1A autoreceptors in female than in male knockout 5-HTT mice. After gonadectomy, the functional status of 5-HT1A autoreceptors was unchanged in wild-type mice, whereas in knockout 5-HTT, castrated males exhibited a down-regulation, and ovariectomized females an up-regulation of these receptors, as shown by electrophysiological recording and autoradiographic labelling in the DRN, as well as by changes in 8-OH-DPAT-induced hypothermia. Finally, in gonadectomized knockout 5-HTT mice, treatment with testosterone or estradiol restored the DRN neuronal firing sensitivity to 8-OH-DPAT back to sham control level in males or females, respectively. These data indicate that sexual hormones participate in the mechanisms responsible for the desensitization of 5-HT1A autoreceptors in knockout 5-HTT mice. The differential effects of testosterone and estradiol on 5-HT1A-mediated control of 5-HT neurotransmission might be related to the well-established gender differences in the vulnerability to depression. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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