The Wake-Promoting Peptide Orexin-B Inhibits Glutamatergic Transmission to Dorsal Raphe Nucleus Serotonin Neurons through Retrograde Endocannabinoid Signaling

Haj‐Dahmane, Samir; Shen, Roh‐Yu

doi:10.1523/jneurosci.3258-04.2005

Cited by 128 publications

(109 citation statements)

References 70 publications

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“…Second, we consider the possible role of the putative CB 3 R or a non-CB 1 cannabinoid receptor possessing a lower affinity to WIN55,212-2 proposed to be present in glutamatergic terminals and thus in a position to inhibit the release of excitatory amino acids (Hajos and Freund, 2002). Indeed, a reduction of evoked glutamate-mediated synaptic currents in 5-HT neurons was observed in acute DR slice preparations (Haj-Dahmane and Shen, 2005). Third, CB 1 R agonists may differentially act on GABAergic and glutamatergic pathways as observed in the ventral tegmental area (VTA) Riegel and Lupica, 2004).…”

Section: Discussionmentioning

confidence: 99%

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Bambico¹,

Katz²,

Debonnel³

et al. 2007

J. Neurosci.

288

213

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Preclinical and clinical studies show that cannabis modulates mood and possesses antidepressant-like properties, mediated by the agonistic activity of cannabinoids on central CB 1 receptors (CB 1 Rs). The action of CB 1 R agonists on the serotonin (5-HT) system, the major transmitter system involved in mood control and implicated in the mechanism of action of antidepressants, remains however poorly understood. In this study, we demonstrated that, at low doses, the CB 1 R agonist WIN55, 212-2 [R(ϩ)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate] exerts potent antidepressant-like properties in the rat forced-swim test (FST). This effect is CB 1 R dependent because it was blocked by the CB 1 R antagonist rimonabant and is 5-HT mediated because it was abolished by pretreatment with the 5-HT-depleting agent parachlorophenylalanine. Then, using in vivo electrophysiology, we showed that low doses of WIN55,212-2 dose dependently enhanced dorsal raphe nucleus 5-HT neuronal activity through a CB 1 R-dependent mechanism. Conversely, high doses of WIN55,212-2 were ineffective in the FST and decreased 5-HT neuronal activity through a CB 1 R-independent mechanism. The CB 1 R agonist-induced enhancement of 5-HT neuronal activity was abolished by total or medial prefrontocortical, but not by lateral prefrontocortical, transection. Furthermore, 5-HT neuronal activity was enhanced by the local microinjection of WIN55,212-2 into the ventromedial prefrontal cortex (mPFCv) but not by the local microinjection of WIN55,212-2 into the lateral prefrontal cortex. Similarly, the microinjection of WIN55,212-2 into the mPFCv produced a CB 1 R-dependent antidepressantlike effect in the FST. These results demonstrate that CB 1 R agonists possess antidepressant-like properties and modulate 5-HT neuronal activity via the mPFCv.

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Section: Discussionmentioning

confidence: 99%

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Bambico¹,

Katz²,

Debonnel³

et al. 2007

J. Neurosci.

288

213

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“…78,79 While orexin activates catecholamines and endocannabinoids, catecholamines and serotonin exert a negative feedback on the orexin system. 80,81 These findings suggest a central role for the orexin systems in the shared biology of feeding and mood disorders.…”

Section: A B C D E F G Hmentioning

confidence: 93%

Approaching the shared biology of obesity and depression: the stress axis as the locus of gene–environment interactions

et al. 2006

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Obesity and depression are serious public health problems and also constitute cardiovascular disease risk factors. Research organizations have called for efforts to explore the interrelationship between obesity and depression. A useful starting point is the fact that in both disorders there is dysregulation of stress systems. We review molecular and clinical evidence indicating that the mediators of the stress response are a key locus for geneenvironment interactions in the shared biology of depression and obesity. Scientific milestones include translational paradigms such as mice knockouts, imaging and pharmacogenomic approaches that can identify new therapeutic strategies for those burdened by these two afflictions of contemporary civilization. Perspectives for the future are promising. Our ability to dissect the underpinnings of common and complex diseases with shared substrates will be greatly enhanced by the Genes and Environment Initiative, the emerging Large Scale Studies of Genes and Environment in Common Disease, and the UK Biobank Project.

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“…To test this prediction, we used the poorly hydrolysable GTP analog GTP␥S, a compound that limits the rate of GTP hydrolysis by G␣ subunits and thus renders G protein-mediated responses irreversible. A previous study has successfully used this strategy to disclose a G proteinmediated release of a cannabinoid retrograde messenger (24).…”

Section: Gtp␥s Selectively Renders Irreversible the 5-ht2ar-induced Imentioning

confidence: 99%

Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex

Béïque¹,

Imad

Mladenovic³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

199

118

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Classic hallucinogens such as lysergic acid diethylamide are thought to elicit their psychotropic actions via serotonin receptors of the 5-hydroxytryptamine 2A subtype (5-HT 2AR). One likely site for these effects is the prefrontal cortex (PFC). Previous studies have shown that activation of 5-HT2ARs in this region results in a robust increase in spontaneous glutamatergic synaptic activity, and these results have led to the widely held idea that hallucinogens elicit their effect by modulating synaptic transmission within the PFC. Here, we combine cellular and molecular biological approaches, including single-cell 5-HT 2ARs inactivation and 5-HT2AR rescue over a 5-HT 2AR knockout genetic background, to distinguish between competing hypotheses accounting for these effects. The results from these experiments do not support the idea that 5-HT 2ARs elicit the release of an excitatory retrograde messenger nor that they activate thalamocortical afferents, the two dominant hypotheses. Rather, they suggest that 5-HT 2ARs facilitate intrinsic networks within the PFC. Consistent with this idea, we locate a discrete subpopulation of pyramidal cells that is strongly excited by 5-HT 2AR activation.gene gun ͉ in vitro electrophysiology ͉ organotypic slices ͉ serotonin ͉ hallucinogen T he idea that classic hallucinogens such as lysergic acid diethylamide and psylocibin act by interfering with serotonergic neurotransmission can be traced to the middle of the 20th century (1). It was, however, not until the 1980s that serotonin receptors of the 5-hydroxytryptamine 2A subtype (5-HT 2A R) were identified as the molecular target for these agents (refs. 2, 3; reviewed in refs. 4, 5). Subsequent brain imaging studies in human subjects have extended these findings to identify the prefrontal cortex (PFC), which is highly enriched in these receptors, as a key brain region in mediating the effects of hallucinogens (6, 7). These findings have led to the now widely accepted view that activation of 5-HT 2A R in the prefrontal is a key biological step leading to the psychological effects of hallucinogens (5, 8).Our understanding of the mechanisms by which 5-HT 2A R activation elicits the sensory and behavioral manifestation of hallucinogens would be enriched by a precise understanding of how these receptors modulate cellular and network excitability in the PFC. To that effect, a number of studies have addressed the electrophysiological effects signaled by 5-HT 2A Rs in this region. There is general concordance that the most robust cellular effect observed in pyramidal cell of the PFC on stimulation of 5-HT 2A Rs involves an increase in both the frequency and amplitude of glutamatergic spontaneous excitatory postsynaptic potentials/spontaneous excitatory postsynaptic currents (sEPSCs) (9)(10)(11)(12)(13)(14). This observation thus points to 5-HT 2A Rs as powerful modulators of the excitability of PFC networks and reconciles evidence implicating both glutamatergic and serotonergic systems in the actions of hallucinogens (15).Although multiple ...

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The Wake-Promoting Peptide Orexin-B Inhibits Glutamatergic Transmission to Dorsal Raphe Nucleus Serotonin Neurons through Retrograde Endocannabinoid Signaling

Cited by 128 publications

References 70 publications

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Approaching the shared biology of obesity and depression: the stress axis as the locus of gene–environment interactions

Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex

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