Early-life stress exacerbates the effects of WIN55,212-2 and modulates the cannabinoid receptor type 1 expression

Martín‐Sánchez, Ana; García-Baos, Alba; Castro‐Zavala, Adriana; Alegre-Zurano, Laia; Valverde, Olga

doi:10.1016/j.neuropharm.2020.108416

Cited by 13 publications

(17 citation statements)

References 105 publications

(146 reference statements)

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“…Furthermore, in healthy humans, changes in eCB plasma levels in response to acute stress were larger in men than in women (Dlugos et al, 2012). Behavioural effects of exogenous cannabinoids may be more or less pronounced dependent on such differences in the eCB system (Martín-Sanchez et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

et al. 2022

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Background: Preclinical research suggests that cannabidiol (CBD) may have therapeutic potential in pathological anxiety. Dosing guidelines to inform future human studies are however lacking. Aim: We aimed to predict the therapeutic window for anxiety-reducing effects of CBD in humans based on preclinical models. Methods: We conducted two systematic searches in PubMed and Embase up to August 2021, into pharmacokinetic (PK) and pharmacodynamic (PD) data of systemic CBD exposure in humans and animals, which includes anxiety-reducing and potential side effects. Risk of bias was assessed with SYRCLE’s RoB tool and Cochrane RoB 2.0. A control group was an inclusion criterion in outcome studies. In human outcome studies, randomisation was required. We excluded studies that co-administered other substances. We used the IB-de-risk tool for a translational integration of outcomes. Results: We synthesised data from 87 studies. For most observations (70.3%), CBD had no effect on anxiety outcomes. There was no identifiable relation between anxiety outcomes and drug levels across species. In all species (humans, mice, rats), anxiety-reducing effects seemed to be clustered in certain concentration ranges, which differed between species. Discussion: A straightforward dosing recommendation was not possible, given variable concentration–effect relations across species, and no consistent linear effect of CBD on anxiety reduction. Currently, these results raise questions about the broad use as a drug for anxiety. Meta-analytic studies are needed to quantitatively investigate drug efficacy, including aspects of anxiety symptomatology. Acute and (sub)chronic dosing studies with integrated PK and PD outcomes are required for substantiated dose recommendations.

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Section: Discussionmentioning

confidence: 99%

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

et al. 2022

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“…We have previously reported that MSEW protocol causes persistent detrimental consequences in offspring development, inducing behavioural and neurobiological alterations 27,28,38 , that also might occur in children whose mother who has experienced PPD 39,40 . Altogether, these findings highlight the importance of a mother-infant relationship for a healthy development of both parts.…”

Section: Discussionmentioning

confidence: 99%

“…Litters of 6 pups were selected. Dams were randomly assigned to one of two rearing conditions: standard nest (SN) and maternal separation with early weaning (MSEW), which was conducted as previously 27,28 . Briefly, MSEW litters were separated from their mothers for 4 h daily between PD 2-5 (09:30–13:30 h) and 8 h daily between PD6-16 (09:30–17:30 h), and then, they were weaned early on PD 17.…”

Section: Methodsmentioning

confidence: 99%

A novel mouse model of postpartum depression and the neurobiological effects of fast-acting antidepressant treatments

García-Baos

Ferreres-Alvarez

Gallego-Landin

et al. 2022

Preprint

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Postpartum depression (PPD) is a severe psychiatric disorder that affects up to 15% of mothers and impairs mother-infant bonding with devastating consequences on the child development and the mother health. Several studies indicate a possible dysregulation of glutamatergic and GABAergic signalling in the corticolimbic system, as well as a downregulation of the allopregnanolone levels in serum of PPD patients. Although brexanolone, an allopregnanolone-based treatment, has recently emerged as fundamental PPD treatment, there is scarce evidence on its neurobiological action mechanism. Moreover, ketamine appears to be a promising antidepressant treatment preventing PPD, nevertheless whether it might be a more effective than allopregnanolone for some patients remain unknown. Therefore, the present study is aimed to evaluate the depressive-like phenotype of postpartum females undergoing maternal separation with early weaning (MSEW) protocol, as well as to compare the effectiveness of ketamine and allopregnanolone treatments. MSEW dams show increased despair-like behaviour, anhedonia and disrupted maternal behaviour. Moreover, lower allopregnanolone serum levels, reduction of vesicular transporters for GABA (VGAT) and glutamate (VGLUT1) in the infralimbic cortex, as well as decreased hippocampal cellular proliferation are found in MSEW females. As for the antidepressant treatments, both drugs prevent despair-like behaviour, whereas only ketamine reverts anhedonia present in MSEW females. In addition, both treatments induce pro-neurogenic effects in the dorsal hippocampus but only allopregnanolone increases the VGAT and VGLUT1, without altering the excitatory/inhibitory ratio. Altogether, we propose a new mice model that recapitulates the core symptomatology and alterations in glutamatergic and GABAergic systems shown in PPD patients, which allows us to investigate the therapeutic mechanisms of allopregnanolone and ketamine.

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Section: Introductionmentioning

confidence: 99%

“…In our laboratory, we use a well-established mouse model of early-life stress known as maternal separation with early weaning (MSEW), (George et al, 2010), which recapitulates the main phenotype observed in depression, such as anhedonia (Gracia-Rubio et al, 2016), social interaction disruption (Portero-Tresserra et al, 2018), despairlike behaviour (Gracia-Rubio et al, 2016) and anxiety-like behaviours (Martín-Sánchez et al, 2021). Moreover, animals exposed to MSEW exhibit a higher vulnerability to drug consumption Portero-Tresserra et al, 2018) as well as alterations in glutamatergic , serotonergic (Gracia-Rubio et al, 2016) and endocannabinoid systems (Martín-Sánchez et al, 2021;Portero-Tresserra et al, 2018). Despite the fact that we observed a sexual dimorphism in several outcomes related to MSEW, depressive-like behaviour and cocaine seeking in the present model (Castro-Zavala et al, 2021), there are no previous reports studying possible brain metabolic capacity alterations in MSEW females, since most of the studies have been developed only in male mice.…”

Section: Introductionmentioning

confidence: 99%

Early-life stress induces emotional and molecular alterations in female mice that are partially reversed by cannabidiol

Martín‐Sánchez

González-Pardo

Alegre-Zurano

et al. 2022

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Early-life stress exacerbates the effects of WIN55,212-2 and modulates the cannabinoid receptor type 1 expression

Cited by 13 publications

References 105 publications

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration–effect relations using the IB-de-risk tool

A novel mouse model of postpartum depression and the neurobiological effects of fast-acting antidepressant treatments

Early-life stress induces emotional and molecular alterations in female mice that are partially reversed by cannabidiol

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