Omega-3 decreases D1 and D2 receptors expression in the prefrontal cortex and prevents amphetamine-induced conditioned place preference in rats

Metz, Vinícia Garzella; Segat, Hecson Jesser; Dias, Verônica Tironi; Barcelos, Raquel Cristine Silva; Maurer, Luana Haselein; Stiebe, Jéssica; Emanuelli, Tatiana; Burger, Marilise Escobar; Pase, Camila Simonetti

doi:10.1016/j.jnutbio.2019.02.007

Cited by 18 publications

(12 citation statements)

References 88 publications

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“…Interestingly, we also reported that DRD1 protein levels measured in the STR and FCx, two brain areas where this receptor is highly expressed [98], are lower in stressed mice receiving saffron than in their untreated counterparts. Akin to these data, a nutritional supplementation with n-3 polyunsaturated fatty acids, which are well-known for their beneficial effects on mood, has been recently shown to improve DA-related behavioral alterations by downregulating DRD1 levels [102]. It may be tempting to similarly propose a link between saffron-induced DRD1 downregulation and improvement of stress-induced depressive-like behavior.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Stress-Induced Depressive-like Behavior by Saffron Extract Is Associated with Modulation of Kynurenine Pathway and Monoamine Neurotransmission

et al. 2021

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Depressive disorders are a major public health concern. Despite currently available treatment options, their prevalence steadily increases, and a high rate of therapeutic failure is often reported, together with important antidepressant-related side effects. This highlights the need to improve existing therapeutic strategies, including by using nutritional interventions. In that context, saffron recently received particular attention for its beneficial effects on mood, although the underlying mechanisms are poorly understood. This study investigated in mice the impact of a saffron extract (Safr’Inside™; 6.25 mg/kg, per os) on acute restraint stress (ARS)-induced depressive-like behavior and related neurobiological alterations, by focusing on hypothalamic–pituitary–adrenal axis, inflammation-related metabolic pathways, and monoaminergic systems, all known to be altered by stress and involved in depressive disorder pathophysiology. When given before stress onset, Safr’Inside administration attenuated ARS-induced depressive-like behavior in the forced swim test. Importantly, it concomitantly reversed several stress-induced monoamine dysregulations and modulated the expression of key enzymes of the kynurenine pathway, likely reducing kynurenine-related neurotoxicity. These results show that saffron pretreatment prevents the development of stress-induced depressive symptoms and improves our understanding about the underlying mechanisms, which is a central issue to validate the therapeutic relevance of nutritional interventions with saffron in depressed patients.

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Section: Discussionmentioning

confidence: 99%

Prevention of Stress-Induced Depressive-like Behavior by Saffron Extract Is Associated with Modulation of Kynurenine Pathway and Monoamine Neurotransmission

et al. 2021

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“…However, it is a strong possibility given findings from two recent studies with fish oil. Specifically, these studies showed that chronic treatment with fish oil, which like sesame oil is rich in essential polyunsaturated fatty acids (Sowmya et al, 2009), prevented the reinstatement of an amphetamine or morphine-induced CPP and associated molecular changes (Metz et al, 2019; Milanesi et al, 2019). Sesame oil is also rich in linoleic acid, which has been reported to have antagonistic effects on ER signaling (Durgam and Fernandes, 1997; Kenny et al, 2000; Tanmahasamut et al, 2004; Liu and Sidell, 2005).…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen Blocks the Development of Motivational Features of an Addiction-Like Phenotype in Female Rats

Bakhti-Suroosh

Nesil

Lynch

2019

Front. Behav. Neurosci.

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Women become addicted sooner after initiating cocaine use as compared to men. Preclinical studies reveal a similar vulnerability in females, with findings from ovariectomized rats suggesting that estradiol mediates the enhanced vulnerability. However, since ovariectomy depletes not only estradiol, but all ovarian hormones, its role in a physiological context is not clear. Thus, the goal of this study was to determine the role of estradiol in the development of an addiction-like phenotype in ovaryintact females treated chronically with the selective estrogen receptor (ER) modulator tamoxifen. We hypothesized that tamoxifen, by antagonizing ERs, would block the development of an addiction-like phenotype as defined by an enhanced motivation for cocaine (assessed under a progressive-ratio schedule), and a heightened vulnerability to relapse (assessed under an extinction/cue-induced reinstatement procedure). Effects were examined following extended access cocaine self-administration (24-h/day; 4discrete trials/h; 1.5 mg/kg/infusion) and 14-days of abstinence, conditions optimized for inducing an addiction-like phenotype. As predicted, motivation for cocaine was increased following extended-access self-administration and protracted abstinence in the vehicle (sesame oil) and no-injection control groups, but not in the tamoxifen group indicating that ER signaling is critical for the development of this feature of an addiction-like phenotype. Surprisingly, the increase in motivation for cocaine following abstinence was also attenuated in the vehicle group as compared to no-injection controls suggesting that oil/injections also affected its development. Contrary to our hypothesis, tamoxifen did not decrease vulnerability to relapse as this group responded at similar levels during initial extinction sessions and cue-induced reinstatement testing as compared to controls. Tamoxifen did, however, impair extinction learning as this group took longer to extinguish as compared to controls. Taken together, these findings indicate that estradiol is critical for the extinction of drug-associated cues and the development of motivational features of addiction.

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“…Amphetamine induces dopaminergic deficits and increases the levels of D1 and D2 receptors, which can be inverted by omega-3 supplementation. Indeed, omega-3 induces a reduction in D1 and D2 receptors levels and an increase in the levels of vesicular monoamine transporter 2, which transfers dopamine from the cytosol to synaptic vesicles in the prefrontal cortex (PFC) [86]. Conversely, an excess of saturated fatty acids, from childhood to adulthood, seems to increase sensibility to amphetamine by increasing the bursting activity of dopaminergic neurons in the mesolimbic pathway [87].…”

Section: Effects Of Omega-3 On the Dopaminergic And Serotonergic Systemsmentioning

confidence: 99%

Shared Biological Pathways between Antipsychotics and Omega-3 Fatty Acids: A Key Feature for Schizophrenia Preventive Treatment?

Frajerman

Scoriels

Kébir

et al. 2021

IJMS

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Schizophrenia typically emerges during adolescence, with progression from an ultra-high risk state (UHR) to the first episode of psychosis (FEP) followed by a chronic phase. The detailed pathophysiology of schizophrenia and the factors leading to progression across these stages remain relatively unknown. The current treatment relies on antipsychotics, which are effective for FEP and chronic schizophrenia but ineffective for UHR patients. Antipsychotics modulate dopaminergic and glutamatergic neurotransmission, inflammation, oxidative stress, and membrane lipids pathways. Many of these biological pathways intercommunicate and play a role in schizophrenia pathophysiology. In this context, research of preventive treatment in early stages has explored the antipsychotic effects of omega-3 supplementation in UHR and FEP patients. This review summarizes the action of omega-3 in various biological systems involved in schizophrenia. Similar to antipsychotics, omega-3 supplementation reduces inflammation and oxidative stress, improves myelination, modifies the properties of cell membranes, and influences dopamine and glutamate pathways. Omega-3 supplementation also modulates one-carbon metabolism, the endocannabinoid system, and appears to present neuroprotective properties. Omega-3 has little side effects compared to antipsychotics and may be safely prescribed for UHR patients and as an add-on for FEP patients. This could to lead to more efficacious individualised treatments, thus contributing to precision medicine in psychiatry.

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Omega-3 decreases D1 and D2 receptors expression in the prefrontal cortex and prevents amphetamine-induced conditioned place preference in rats

Cited by 18 publications

References 88 publications

Prevention of Stress-Induced Depressive-like Behavior by Saffron Extract Is Associated with Modulation of Kynurenine Pathway and Monoamine Neurotransmission

Prevention of Stress-Induced Depressive-like Behavior by Saffron Extract Is Associated with Modulation of Kynurenine Pathway and Monoamine Neurotransmission

Tamoxifen Blocks the Development of Motivational Features of an Addiction-Like Phenotype in Female Rats

Shared Biological Pathways between Antipsychotics and Omega-3 Fatty Acids: A Key Feature for Schizophrenia Preventive Treatment?

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