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Article: Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions.

Fogaça, Manoela V / Duman, Ronald S

2019 Volume 13, Page(s) 87

Abstract: Major depressive disorder (MDD) is a debilitating illness characterized by neuroanatomical and functional alterations in limbic structures, notably the prefrontal cortex (PFC), that can be precipitated by exposure to chronic stress. For decades, the ... ...

Abstract	Major depressive disorder (MDD) is a debilitating illness characterized by neuroanatomical and functional alterations in limbic structures, notably the prefrontal cortex (PFC), that can be precipitated by exposure to chronic stress. For decades, the monoaminergic deficit hypothesis of depression provided the conceptual framework to understand the pathophysiology of MDD. However, accumulating evidence suggests that MDD and chronic stress are associated with an imbalance of excitation-inhibition (E:I) within the PFC, generated by a deficit of inhibitory synaptic transmission onto principal glutamatergic neurons. MDD patients and chronically stressed animals show a reduction in GABA and GAD67 levels in the brain, decreased expression of GABAergic interneuron markers, and alterations in GABA
Language	English
Publishing date	2019-03-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2019.00087
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Article ; Online: M1 acetylcholine receptors in somatostatin interneurons contribute to GABAergic and glutamatergic plasticity in the mPFC and antidepressant-like responses.

Fogaça, Manoela V / Wu, Min / Li, Chan / Li, Xiao-Yuan / Duman, Ronald S / Picciotto, Marina R

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2023 Volume 48, Issue 9, Page(s) 1277–1287

Abstract: Alterations in glutamatergic and GABAergic function in the medial prefrontal cortex (mPFC) are prevalent in individuals with major depressive disorder, resulting in impaired synaptic plasticity that compromises the integrity of signal transfer to limbic ... ...

Abstract	Alterations in glutamatergic and GABAergic function in the medial prefrontal cortex (mPFC) are prevalent in individuals with major depressive disorder, resulting in impaired synaptic plasticity that compromises the integrity of signal transfer to limbic regions. Scopolamine, a non-selective muscarinic receptor antagonist, produces rapid antidepressant-like effects by targeting M1-type acetylcholine receptors (M1R) on somatostatin (SST) interneurons. So far, these effects have been investigated with relatively short-term manipulations, and long-lasting synaptic mechanisms involved in these responses are still unknown. Here, we generated mice with conditional deletion of M1R (M1
MeSH term(s)	Mice ; Male ; Animals ; Depressive Disorder, Major/drug therapy ; Interneurons/physiology ; Antidepressive Agents/therapeutic use ; Scopolamine/pharmacology ; Receptors, Cholinergic/metabolism ; Receptors, Cholinergic/therapeutic use ; Somatostatin/metabolism ; Prefrontal Cortex
Chemical Substances	Antidepressive Agents ; Scopolamine (DL48G20X8X) ; Receptors, Cholinergic ; Somatostatin (51110-01-1)
Language	English
Publishing date	2023-05-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-023-01583-7
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Article ; Online: The synergistic mechanism of action of Dajianzhong decoction in conjunction with ketamine in the treatment of depression.

Li, Chan / Zhang, Jiping / Liu, Hanhe / Yuan, Huijie / Cai, Jianxin / Fogaça, Manoela V / Zhang, Yuan-Wei

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 165, Page(s) 115137

Abstract: Depression is a multifactorial syndrome with a variety of underlying pathological mechanisms. While ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, exhibits a rapid antidepressant action in the central never system (CNS), the potential ... ...

Abstract	Depression is a multifactorial syndrome with a variety of underlying pathological mechanisms. While ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, exhibits a rapid antidepressant action in the central never system (CNS), the potential addiction and psychotomimetic adverse effects of ketamine limit its chronic use in clinical practice. Therefore, it is necessary to discover an additional agent that shows a synergistic antidepressant activity with ketamine to sustain its therapeutic action so as to reduce its use frequency in depression treatment. The present study indicated that Dajianzhong decoction (DJZT), an empirical herbal formula used for the clinical treatment of several inflammation-related intestinal disorders, sustains behavioral and synaptic action of ketamine in depressive mouse models. Additionally, ketamine was also demonstrated to exert a synergistic action with DJZT to alleviate the chronic unpredictable mild stress (CUMS)-induced abnormalities in gut barrier proteins and colonic histology, and subsequently to normalize the diversity and composition of gut microbiota. Furthermore, DJZT was shown to possess an anti-inflammatory activity to prevent activation of NF-κB from releasing proinflammatory cytokines, specifically through inhibiting Th17 cells/IL-17A pathway. Our results uncovered the mechanism of action of DJZT in conjunction with ketamine in depression treatment by which these agents target different pathological factors across biological systems and exert a synergistic activity through a bidirectional communication in the gut-brain axis, and also provided new insights into the systematic treatment of depression.
MeSH term(s)	Mice ; Animals ; Ketamine/pharmacology ; Ketamine/therapeutic use ; Depression/drug therapy ; Depression/metabolism ; Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use ; Cytokines/metabolism ; NF-kappa B/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism
Chemical Substances	Ketamine (690G0D6V8H) ; Antidepressive Agents ; Cytokines ; NF-kappa B ; Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2023-07-14
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.115137
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Ud II Zs.198: Show issues

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Article ; Online: Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function.

Duman, Ronald S / Shinohara, Ryota / Fogaça, Manoela V / Hare, Brendan

Molecular psychiatry

2019 Volume 24, Issue 12, Page(s) 1816–1832

Abstract: Efforts to develop efficacious antidepressant agents with novel mechanisms have been largely unsuccessful since the 1950's until the discovery of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist that produces rapid and sustained ... ...

Abstract	Efforts to develop efficacious antidepressant agents with novel mechanisms have been largely unsuccessful since the 1950's until the discovery of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist that produces rapid and sustained antidepressant actions even in treatment-resistant patients. This finding has ushered in a new era for the development of novel rapid-acting antidepressants that act at the NMDA receptor complex, but without dissociative and psychotomimetic side effects of ketamine. Here, we review the current state of rapid-acting antidepressant drug development, including NMDA channel blockers, glycine site agents, and allosteric modulators, as well as ketamine stereoisomers and metabolites. In addition, we focus on the neurobiological mechanisms underlying the actions of these diverse agents and discuss evidence of convergent mechanisms including increased brain-derived neurotrophic factor signaling, increased synthesis of synaptic proteins, and most notably increased GluR1 and synaptic connectivity in the medial prefrontal cortex. These convergent mechanisms provide insight for potential additional novel targets for drug development (e.g., agents that increase synaptic protein synthesis and plasticity). Importantly, the convergent effects on synapse formation and plasticity also reverse the well-documented neuronal and synaptic deficits associated with stress and depression, and thereby target the underlying pathophysiology of major depressive disorder.
MeSH term(s)	Animals ; Antidepressive Agents/metabolism ; Antidepressive Agents/pharmacology ; Depression/drug therapy ; Depressive Disorder, Major/drug therapy ; Glutamic Acid/metabolism ; Humans ; Ketamine/pharmacology ; Neurobiology/methods ; Neurogenesis/drug effects ; Neurons/metabolism ; Receptors, AMPA/drug effects ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/drug effects ; Receptors, N-Methyl-D-Aspartate/metabolism ; Signal Transduction/drug effects ; Synapses/metabolism ; Synaptic Transmission/drug effects
Chemical Substances	Antidepressive Agents ; Receptors, AMPA ; Receptors, N-Methyl-D-Aspartate ; Glutamic Acid (3KX376GY7L) ; Ketamine (690G0D6V8H)
Language	English
Publishing date	2019-03-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-019-0400-x
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Zs.A 4812: Show issues

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Article ; Online: Behavioral effects induced by the cannabidiol analogs HU-502 and HU-556.

Colodete, Débora A E / Silva, Nicole R / Pedrazzi, João Francisco C / Fogaça, Manoela V / Cortez, Isadora / Del-Bel, Elaine A / Breuer, Aviva / Mechoulam, Raphael / Gomes, Felipe V / Guimarães, Francisco S

Behavioural pharmacology

2023 Volume 34, Issue 4, Page(s) 213–224

Abstract: Cannabidiol is a phytocannabinoid that lacks the psychotomimetic properties of Δ9-tetrahydrocannabinol (THC), the main psychoactive Cannabis sativa component. Cannabidiol has several potential therapeutic properties, including anxiolytic, antidepressant, ...

Abstract	Cannabidiol is a phytocannabinoid that lacks the psychotomimetic properties of Δ9-tetrahydrocannabinol (THC), the main psychoactive Cannabis sativa component. Cannabidiol has several potential therapeutic properties, including anxiolytic, antidepressant, and antipsychotic; however, cannabidiol has low oral bioavailability, which can limit its clinical use. Here, we investigated if two cannabidiol analogs, HU-502 and HU-556, would be more potent than cannabidiol in behavioral tests predictive of anxiolytic, antidepressant, and antipsychotic effects. Different doses (0.01-3 mg/kg; intraperitoneally) of HU-556 and HU-502 were tested in male Swiss mice submitted to the elevated plus maze (EPM), forced swimming test (FST), and amphetamine-induced-prepulse inhibition (PPI) disruption and hyperlocomotion. Cannabidiol is effective in these tests at a dose range of 15-60 mg/kg in mice. We also investigated if higher doses of HU-556 (3 and 10 mg/kg) and HU-502 (10 mg/kg) produced the cannabinoid tetrad (hypolocomotion, catalepsy, hypothermia, and analgesia), which is induced by THC-like compounds. HU-556 (0.1 and 1 mg/kg) increased the percentage of open arm entries (but not time) in the EPM, decreased immobility time in the FST, and attenuated amphetamine-induced PPI disruption. HU-502 (1 and 3 mg/kg) decreased amphetamine-induced hyperlocomotion and PPI impairment. HU-556, at high doses, caused catalepsy and hypolocomotion, while HU-502 did not. These findings suggest that similar to cannabidiol, HU-556 could induce anxiolytic, antidepressant, and antipsychotic-like effects and that HU-502 has antipsychotic properties. These effects were found at a dose range devoid of cannabinoid tetrad effects.
MeSH term(s)	Mice ; Male ; Animals ; Cannabidiol/pharmacology ; Antipsychotic Agents/pharmacology ; Anti-Anxiety Agents/pharmacology ; Catalepsy/chemically induced ; Cannabinoids ; Antidepressive Agents/pharmacology ; Amphetamine ; Dronabinol/pharmacology
Chemical Substances	Cannabidiol (19GBJ60SN5) ; Antipsychotic Agents ; Anti-Anxiety Agents ; Cannabinoids ; Antidepressive Agents ; Amphetamine (CK833KGX7E) ; Dronabinol (7J8897W37S)
Language	English
Publishing date	2023-05-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1027374-8
ISSN	1473-5849 ; 0955-8810
ISSN (online)	1473-5849
ISSN	0955-8810
DOI	10.1097/FBP.0000000000000727
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Zs.A 2883: Show issues

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Article ; Online: Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses.

Fogaça, Manoela V / Wu, Min / Li, Chan / Li, Xiao-Yuan / Picciotto, Marina R / Duman, Ronald S

Molecular psychiatry

2020 Volume 26, Issue 7, Page(s) 3277–3291

Abstract: Major depressive disorder (MDD) is associated with alterations of GABAergic interneurons, notably somatostatin (Sst) as well as parvalbumin (Pvalb), in cortical brain areas. In addition, the antidepressant effects of rapid-acting drugs are thought to ... ...

Abstract	Major depressive disorder (MDD) is associated with alterations of GABAergic interneurons, notably somatostatin (Sst) as well as parvalbumin (Pvalb), in cortical brain areas. In addition, the antidepressant effects of rapid-acting drugs are thought to occur via inhibition of GABA interneurons. However, the impact of these interneuron subtypes in affective behaviors as well as in the effects of rapid-acting antidepressants remains to be determined. Here, we used a Cre-dependent DREADD-chemogenetic approach to determine if inhibition of GABA interneurons in the mPFC of male mice is sufficient to produce antidepressant actions, and conversely if activation of these interneurons blocks the rapid and sustained antidepressant effects of scopolamine, a nonselective acetylcholine muscarinic receptor antagonist. Chemogenetic inhibition of all GABA interneurons (Gad1+), as well as Sst+ and Pvalb+ subtypes in the mPFC produced dose and time-dependent antidepressant effects in the forced swim and novelty suppressed feeding tests, and increased synaptic plasticity. In contrast, stimulation of Gad1, Sst, or Pvalb interneurons in mPFC abolished the effects of scopolamine and prevented scopolamine induction of synaptic plasticity. The results demonstrate that transient inhibition of GABA interneurons promotes synaptic plasticity that underlies rapid antidepressant responses.
MeSH term(s)	Animals ; Antidepressive Agents/therapeutic use ; Depressive Disorder, Major/drug therapy ; Interneurons/drug effects ; Male ; Mice ; Parvalbumins ; Prefrontal Cortex/drug effects ; gamma-Aminobutyric Acid
Chemical Substances	Antidepressive Agents ; Parvalbumins ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2020-10-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-020-00916-y
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Zs.A 4812: Show issues

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Article ; Online: Prefrontal cortex interneurons display dynamic sex-specific stress-induced transcriptomes.

Girgenti, Matthew J / Wohleb, Eric S / Mehta, Sameet / Ghosal, Sriparna / Fogaca, Manoela V / Duman, Ronald S

Translational psychiatry

2019 Volume 9, Issue 1, Page(s) 292

Abstract: γ-aminobutyric acid (GABA) inhibitory interneurons play a key role in efferent and afferent control of principle neuron activity in the prefrontal cortex (PFC), thereby regulating signal integrity of cognitive and behavioral processes. Recent evidence ... ...

Abstract	γ-aminobutyric acid (GABA) inhibitory interneurons play a key role in efferent and afferent control of principle neuron activity in the prefrontal cortex (PFC), thereby regulating signal integrity of cognitive and behavioral processes. Recent evidence suggests that specific subtypes of interneurons in the PFC mediate stress-induced depressive-like behaviors. Abnormalities of GABA interneurons, particularly the somatostatin (human, SST; mouse, Sst) subtype, have been reported in postmortem brains of depressed subjects and include sex differences that could explain the increased incidence of depression in women. Here, we analyze the transcriptional profiles and the effects of chronic stress in males vs. females on GABA interneuron subtypes in the PFC. Using Sst- and Parvalbumin-fluorescence tagged reporter mice and fluorescence-activated cell sorting (FACS) combined with RNA sequencing, we identify distinct transcriptome profiles for these interneuron subtypes in the medial PFC. Based on evidence that SST interneurons are altered in depression, we then determined the effects of chronic stress on this interneuron subtype. Chronic stress causes significant dysregulation of several key pathways, including sex-specific differences in the Sst interneuron profiles. The transcriptional pathways altered by chronic stress in males overlap with enriched pathways in non-stressed females. These changes occurred predominantly in decreased expression of elongation initiation factor 2 (EIF2) signaling, suggesting that dysfunction of the translational machinery of SST interneurons could be critical to the development of depressive-like behaviors in males. In addition, SST interneurons from females exposed to chronic stress show dysregulation of different, growth factor signaling pathways.
MeSH term(s)	Animals ; Female ; Interneurons/metabolism ; Male ; Mice ; Nerve Net/metabolism ; Nerve Net/pathology ; Parvalbumins/metabolism ; Prefrontal Cortex/cytology ; Prefrontal Cortex/pathology ; Sex Factors ; Somatostatin/metabolism ; Stress, Psychological/pathology ; Transcriptome ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	Parvalbumins ; Somatostatin (51110-01-1) ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2019-11-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-019-0642-z
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Article ; Online: The endocannabinoid, endovanilloid and nitrergic systems could interact in the rat dorsolateral periaqueductal gray matter to control anxiety-like behaviors.

Batista, Priscila A / Fogaça, Manoela V / Guimarães, Francisco S

Behavioural brain research

2015 Volume 293, Page(s) 182–188

Abstract: Cannabinoid compounds usually produce biphasic effects in the modulation of emotional responses. Low doses of the endocannabinoid anandamide (AEA) injected into the dorsolateral periaqueductal gray matter (dlPAG) induce anxiolytic-like effects via CB1 ... ...

Abstract	Cannabinoid compounds usually produce biphasic effects in the modulation of emotional responses. Low doses of the endocannabinoid anandamide (AEA) injected into the dorsolateral periaqueductal gray matter (dlPAG) induce anxiolytic-like effects via CB1 receptors activation. However, at higher doses the drug loses this effect, in part by activating Transient Receptor Potential Vanilloid Type 1 (TRPV1). Activation of these latter receptors could induce the formation of nitric oxide (NO). Thus, the present study tested the hypothesis that at high doses AEA loses it anxiolytic-like effect by facilitating, probably via TRPV1 receptor activation, the formation of NO. Male Wistar rats received combined injections into the dlPAG of vehicle, the TRPV1 receptor antagonist 6-iodo-nordihydrocapsaicin or the NO scavenger carboxy-PTIO (c-PTIO), followed by vehicle or AEA, and were submitted to the elevated plus maze (EPM) or the Vogel conflict test (VCT). A low dose (5pmol) of AEA produced an anxiolytic-like effect that disappeared at higher doses (50 and 200pmol). The anxiolytic-like effects of these latter doses, however, were restored after pre-treatment with a low and ineffective dose of c-PTIO in both animal models. In addition, the combined administration of ineffective doses of 6-iodo-nordihydrocapsaicin (1nmol) and c-PTIO (0.3nmol) produced an anxiolytic-like response. Therefore, these results support the hypothesis that intra-dlPAG injections of high doses of AEA lose their anxiolytic effects by favoring TRPV1 receptors activity and consequent NO formation, which in turn could facilitate defensive responses.
MeSH term(s)	Animals ; Anxiety/drug therapy ; Anxiety/pathology ; Arachidonic Acids/pharmacology ; Cannabinoid Receptor Agonists/pharmacology ; Capsaicin/analogs & derivatives ; Capsaicin/pharmacology ; Cyclic N-Oxides/pharmacology ; Disease Models, Animal ; Drinking/drug effects ; Drug Interactions ; Endocannabinoids/metabolism ; Endocannabinoids/pharmacology ; Free Radical Scavengers/pharmacology ; Imidazoles/pharmacology ; Male ; Maze Learning/drug effects ; Microinjections ; Nitric Oxide/metabolism ; Periaqueductal Gray/drug effects ; Periaqueductal Gray/metabolism ; Polyunsaturated Alkamides/pharmacology ; Rats ; Rats, Wistar ; Reaction Time/drug effects ; TRPV Cation Channels/metabolism
Chemical Substances	Arachidonic Acids ; Cannabinoid Receptor Agonists ; Cyclic N-Oxides ; Endocannabinoids ; Free Radical Scavengers ; Imidazoles ; Polyunsaturated Alkamides ; TRPV Cation Channels ; Trpv1 protein, rat ; 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (18390-00-6) ; Nitric Oxide (31C4KY9ESH) ; nordihydrocapsaicin (RF657P8DA8) ; Capsaicin (S07O44R1ZM) ; anandamide (UR5G69TJKH)
Language	English
Publishing date	2015-10-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	449927-x
ISSN	1872-7549 ; 0166-4328
ISSN (online)	1872-7549
ISSN	0166-4328
DOI	10.1016/j.bbr.2015.07.019
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Zs.A 1599: Show issues

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Article ; Online: Medial PFC AMPA receptor and BDNF signaling are required for the rapid and sustained antidepressant-like effects of 5-HT

Fukumoto, Kenichi / Fogaça, Manoela V / Liu, Rong-Jian / Duman, Catharine H / Li, Xiao-Yuan / Chaki, Shigeyuki / Duman, Ronald S

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2020 Volume 45, Issue 10, Page(s) 1725–1734

Abstract: We previously reported that the serotonergic system is important for the antidepressant-like effects of ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, which produces rapid and long-lasting antidepressant effects in patients with ... ...

Abstract	We previously reported that the serotonergic system is important for the antidepressant-like effects of ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, which produces rapid and long-lasting antidepressant effects in patients with major depressive disorder (MDD). In particular, selective stimulation of the 5-HT
MeSH term(s)	Animals ; Antidepressive Agents/pharmacology ; Brain-Derived Neurotrophic Factor/metabolism ; Depression/drug therapy ; Depressive Disorder, Major/drug therapy ; Female ; Humans ; Mice ; Prefrontal Cortex/metabolism ; Receptor, Serotonin, 5-HT1A ; Receptors, AMPA
Chemical Substances	Antidepressive Agents ; Brain-Derived Neurotrophic Factor ; Receptors, AMPA ; Receptor, Serotonin, 5-HT1A (112692-38-3)
Language	English
Publishing date	2020-05-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-020-0705-0
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Zs.A 2379: Show issues

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Article ; Online: The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling.

Fogaça, Manoela V / Campos, Alline C / Coelho, Ludmila D / Duman, Ronald S / Guimarães, Francisco S

Neuropharmacology

2018 Volume 135, Page(s) 22–33

Abstract: Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood ... ...

Abstract	Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids. Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB
MeSH term(s)	Amidohydrolases/metabolism ; Animals ; Anti-Anxiety Agents/pharmacology ; Behavior, Animal/drug effects ; Cannabidiol/pharmacology ; Disks Large Homolog 4 Protein ; Glycogen Synthase Kinase 3 beta/metabolism ; Hippocampus/cytology ; Indoles/pharmacology ; Male ; Mice ; Neurogenesis/drug effects ; Neuronal Plasticity/drug effects ; Piperazines ; Piperidines/pharmacology ; Proto-Oncogene Proteins c-akt ; Pyrazoles/pharmacology ; Pyridines ; Receptor, Cannabinoid, CB1/antagonists & inhibitors ; Receptor, Cannabinoid, CB2/antagonists & inhibitors ; Receptors, Metabotropic Glutamate/metabolism ; Serotonin 5-HT1 Receptor Antagonists/pharmacology ; Stress, Psychological/metabolism ; Stress, Psychological/prevention & control ; Synapsins/metabolism
Chemical Substances	Anti-Anxiety Agents ; Disks Large Homolog 4 Protein ; Dlg4 protein, mouse ; Indoles ; Piperazines ; Piperidines ; Pyrazoles ; Pyridines ; Receptor, Cannabinoid, CB1 ; Receptor, Cannabinoid, CB2 ; Receptors, Metabotropic Glutamate ; Serotonin 5-HT1 Receptor Antagonists ; Synapsins ; metabotropic glutamate receptor type 1 ; Cannabidiol (19GBJ60SN5) ; AM 251 (3I4FA44MAI) ; N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide (71IH826FEG) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Gsk3b protein, mouse (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Amidohydrolases (EC 3.5.-) ; fatty-acid amide hydrolase (EC 3.5.1.-) ; iodopravadoline (U1LNJ6NBKA)
Language	English
Publishing date	2018-03-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2018.03.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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