scholarly journals Adaptive Changes in the Sensitivity of the Dorsal Raphe and Hypothalamic Paraventricular Nuclei to Acute Exercise, and Hippocampal Neurogenesis May Contribute to the Antidepressant Effect of Regular Treadmill Running in Rats

Author(s):  
Ayu Nishii ◽  
Seiichiro Amemiya ◽  
Natsuko Kubota ◽  
Takeshi Nishijima ◽  
Ichiro Kita
2019 ◽  
Author(s):  
Xiaotao Li

AbstractBackgroundLight therapy is frequently demonstrated by clinical trials to be effective to seasonal or non-seasonal major depression. However, the pathway underlying the light effect on mood remains unclear. Since a retino-raphe pathway was previously indicated to modulate 5-HT production, we hypothesize that the retinal projection into dorsal raphe nucleus (DRN) may play an important role in the light therapy for depression.MethodsA rat model of 14-day corticosterone administration (40 mg/kg/day subcutaneous injection) was mainly used to test the effect of light therapy on non-seasonal depressant-like behavior, and the involved neural circuitry and neurochemistry as well.ResultsBehavior results revealed that the bright light therapy especially with the blue light of 470 nm and 400 lux, effectively reversed the depression-like responses in those stressed rats. After elimination of retino-raphe projection using immunotoxin (Saporin) the effect of light therapy was significantly attenuated. Whereas activation of retino-raphe projection using HM3q chemogenetics was shown an effect similar to fluoxetine treatment. Furthermore, 5-HT3A positive GABA cells in the DRN were activated with high c-Fos expression that involved in an inhibition of 5-HT synthesis and a subsequent depressive behavior. While light therapy through retino-raphe projection deactivated the hyperaction of those GABA cells in the DRN; that eventually contributed to the antidepressant effect from light therapy.ConclusionsOur results indicate that the retino-raphe circuitry engaged antidepressant effect in DRN that contributed to the light therapy to the non-seasonal depression. 5-HT3A positive GABA cells in DRN was indicated to mediate this function of retino-raphe projection.


2020 ◽  
Author(s):  
Cyrine Hmaied ◽  
Stanislav Koulchitsky ◽  
Ivan Gladwyn-Ng ◽  
Vincent Seutin

ABSTRACTAlthough the fast antidepressant effect of ketamine is now well established clinically, neither its mechanism(s) nor its main site(s) of action is clearly defined. Because enhanced serotoninergic (5-HT) transmission is an important part of the antidepressant effect of various drug classes, we asked whether ketamine and one of its metabolites (hydroxynorketamine [HNK]), both used in their racemic form, may modulate the excitatory drive onto these neurons.Using whole-cell recordings from pharmacologically identified 5-HT and non-5-HT neurons in juvenile rat dorsal raphe slices, we found that both ketamine and HNK (10 µM) increase excitatory AMPA neurotransmission onto a subset (50%) of 5-HT neurons, whereas other 5-HT cells were unaffected. Both compounds increased the amplitude as well as the frequency of spontaneous excitatory post-synaptic currents (sEPSCs) mediated by AMPA receptors. The effect of ketamine was more robust than the one of HNK, since it significantly enhanced the charge transfer through AMPA channels, whereas HNK did not. The increase in the excitatory drive induced by ketamine was dependent on NMDA receptor blockade. In the presence of tetrodotoxin, the effect of ketamine was markedly reduced. Non-5-HT neurons, on the other hand, were unaffected by the drugs.We conclude that ketamine and HNK increase the excitatory drive onto a subset of 5-HT neurons by promoting glutamate release and possibly also through a postsynaptic action. The effect of ketamine is dependent on NMDA receptor modulation and appears to involve a network effect. These findings improve our understanding of the fast-acting antidepressant effect of ketamine.SIGNIFICANCE STATEMENTThe mechanisms of ketamine’s antidepressant effect are currently controversial. We asked whether the drug would produce changes is the strength of synaptic inputs onto serotoninergic neurons of the dorsal raphe. We found that this is indeed the case in about half of these neurons. The action of ketamine was mimicked to some extent by its well-known metabolite hydroxynorketamine, was dependent on NMDA receptor activation and probably involved a local network effect. It remains to be determined if the differential susceptibility of serotoninergic neurons to the drug correlates with any differential inputs and/or outputs.


2010 ◽  
Vol 473 (2) ◽  
pp. 136-140 ◽  
Author(s):  
Ali Jahanshahi ◽  
Lee Wei Lim ◽  
Harry W.M. Steinbusch ◽  
Veerle Visser-Vandewalle ◽  
Yasin Temel

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A12-A12
Author(s):  
Jianhua Zhang ◽  
Mingchu Xi ◽  
Simon Fung ◽  
Charles Tobin ◽  
Sharon Sampogna ◽  
...  

Abstract Introduction Our previous study has shown that there is a direct connection between GABAergic neurons in the nucleus pontis oralis (NPO) and neurons of the dorsal raphe nucleus (DR), providing a morphological basis for the hypothesis that GABAergic inhibitory processes in NPO play an important role in the generation and maintenance of wakefulness as well as active (REM) sleep through the interaction with neurons in the DR. However, the target of such a GABAergic projection from the NPO within the DR is unknown. In the present study, a double-fluorescent labeling technique was employed to examine the target of GABAergic inputs to the DR. Methods Adult cats were deeply anesthetized and perfused transcardially. Subsequently, the brainstem containing the DR was removed, postfixed and cut into 15 μm coronal sections with a Reichert-Jung cryostat. The sections were immunostained with antibodies against GABA-A or GABA-B receptors and GABA following the procedure of double fluorescence immunohistochemistry. Results Under fluorescence microscopy, a large number of neurons were labeled with antibodies against either GABA-A receptor or GABA-B receptor. In addition, neurons labeled with antibody against GABA were observed in the DR. With double fluorescence immunohistochemical techniques, some neurons labeled by anti-GABA antibody were also stained with antibodies against GABA-A or GABA-B receptors. Conclusion The expression of GABA-A or GABA-B receptors by GABAergic neurons in the DR indicates that GABAergic neurons in the DR receive GABAergic inputs. Our previous study has demonstrated that these GABAergic inputs are from the NPO. These data provide a morphological foundation to support our hypothesis that, during wakefulness, NPO GABAergic “Executive” neurons suppress “Second-Order” GABAergic neurons in the DR, which, in turn, activate (disinhibit) serotonergic wake-on neurons in this nucleus. Support (if any) NS092383


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aude Muzerelle ◽  
Mariano Soiza-Reilly ◽  
Cornelia Hainer ◽  
Pierre-Louis Ruet ◽  
Klaus-Peter Lesch ◽  
...  

AbstractProper maternal care is an essential factor of reproductive success in mammals, involving a repertoire of behaviors oriented toward the feeding and care of the offspring. Among the neurotransmitters involved in the initiation of these behaviors, serotonin (5-HT) seems to play an important role. Here we compared pup-oriented maternal behaviors in mice with constitutive 5-HT depletion, the tryptophan hydroxylase 2-knock-out (Tph2-KO) and the Pet1-KO mice. We report that the only common pup-oriented defect in these 2 hyposerotoninergic models is a defective nursing in parturient mice and altered nursing-like (crouching) behavior in virgin mice, while pup retrieval defects are only present in Tph2-KO. Despite a normal mammary gland development and milk production, the defect in appropriate nursing is responsible for severe growth retardation and early lethality of pups born to hyposerotonergic dams. This nursing defect is due to acute rather constitutive 5-HT depletion, as it is reproduced by adult knockdown of Tph2 in the dorsal raphe nucleus in mothers with a prior normal maternal experience. We conclude that 5-HT innervation from the dorsal raphe is required for both the initiation and maintenance of a normal nursing behavior. Our findings may be related to observations of reduced maternal/infant interactions in human depression.


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