Palmitoylethanolamide: From endogenous cannabimimetic substance to innovative medicine for the treatment of cannabis dependence

Coppola, Maurizio; Mondola, Raffaella

doi:10.1016/j.mehy.2013.07.016

Cited by 9 publications

(4 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Growing evidence indicates that OEA and PEA may have neuroprotective properties in neurological disorders such as stroke ( Sun et al, 2007 ; Zhou et al, 2012 ; Ahmad et al, 2012a ), traumatic brain injury ( Ahmad et al, 2012b ), Parkinson′s disease ( Gonzalez-Aparicio et al, 2013 ; Gonzalez-Aparicio and Moratalla, 2013 ), or addiction ( Melis et al, 2008 ; Plaza-Zabala et al, 2010 ; Bilbao et al, 2013 ; Coppola and Mondola, 2013 ). Some of the mechanisms implicated are the modulation of antioxidant responses, neuroinflammation, glial cell proliferation/differentiation, neurogenesis, and neurotransmission.…”

Section: Introductionmentioning

confidence: 99%

Systemic Administration of Oleoylethanolamide Protects from Neuroinflammation and Anhedonia Induced by LPS in Rats

Sayd

Antón

Alén

et al. 2014

International Journal of Neuropsychopharmacology

View full text Add to dashboard Cite

Background:The acylethanolamides oleoylethanolamide and palmitoylethanolamide are endogenous lipid mediators with proposed neuroprotectant properties in central nervous system (CNS) pathologies. The precise mechanisms remain partly unknown, but growing evidence suggests an antiinflammatory/antioxidant profile.Methods:We tested whether oleoylethanolamide/palmitoylethanolamide (10mg/kg, i.p.) attenuate neuroinflammation and acute phase responses (hypothalamus-pituitary-adrenal (HPA) stress axis stress axis activation, thermoregulation, and anhedonia) induced by lipopolysaccharide (0.5mg/kg, i.p.) in rats.Results:Lipopolysaccharide increased mRNA levels of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6, nuclear transcription factor-κB activity, and the expression of its inhibitory protein IκBα in cytoplasm, the inducible isoforms of nitric oxide synthase and cyclooxygenase-2, microsomal prostaglandin E2 synthase mRNA, and proinflammatory prostaglandin E2 content in frontal cortex 150 minutes after administration. As a result, the markers of nitrosative/oxidative stress nitrites (NO2 -) and malondialdehyde were increased. Pretreatment with oleoylethanolamide/ palmitoylethanolamide reduced plasma tumor necrosis factor-α levels after lipopolysaccharide, but only oleoylethanolamide significantly reduced brain tumor necrosis factor-α mRNA. Oleoylethanolamide and palmitoylethanolamide prevented lipopolysaccharide-induced nuclear transcription factor-κB (NF-κB)/IκBα upregulation in nuclear and cytosolic extracts, respectively, the expression of inducible isoforms of nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E2 synthase and the levels of prostaglandin E2. Additionally, both acylethanolamides reduced lipopolysaccharide-induced oxidative/nitrosative stress. Neither oleoylethanolamide nor palmitoylethanolamide modified plasma corticosterone levels after lipopolysaccharide, but both acylethanolamides reduced the expression of hypothalamic markers of thermoregulation interleukin-1β, cyclooxygenase-2, and prostaglandin E2, and potentiated the hypothermic response after lipopolysaccharide. Interestingly, only oleoylethanolamide disrupted lipopolysaccharide-induced anhedonia in a saccharine preference test.Conclusions:Results indicate that oleoylethanolamide and palmitoylethanolamide have antiinflammatory/neuroprotective properties and suggest a role for these acylethanolamides as modulators of CNS pathologies with a neuroinflammatory component.

show abstract

Section: Introductionmentioning

confidence: 99%

Systemic Administration of Oleoylethanolamide Protects from Neuroinflammation and Anhedonia Induced by LPS in Rats

Sayd

Antón

Alén

et al. 2014

International Journal of Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…On the other hand, it is widely accepted that this PEA formulation is involved in the modulation of neuroinflammation produced in the central nervous system (Sayd et al, 2014 ). It has shown to be useful in the control of neuropathic pain (Re et al, 2007 ) and it could exert neuroprotective properties in neurological disorders such as stroke (Ahmad et al, 2012b ), traumatic brain injury (Ahmad et al, 2012a ), Alzheimer and Parkinson's disease (D'Agostino et al, 2012 ; Esposito et al, 2012 ) or addiction (Coppola and Mondola, 2013 ).…”

Section: Methodsmentioning

confidence: 99%

Palmitoylethanolamide Ameliorates Hippocampal Damage and Behavioral Dysfunction After Perinatal Asphyxia in the Immature Rat Brain

et al. 2018

View full text Add to dashboard Cite

Perinatal asphyxia (PA) is an obstetric complication associated with an impaired gas exchange. This health problem continues to be a determinant of neonatal mortality and neurodevelopmental disorders. Palmitoylethanolamide (PEA) has exerted neuroprotection in several models of brain injury and neurodegeneration. We aimed at evaluating the potential neuroprotective role of PEA in an experimental model, which induces PA in the immature rat brain. PA was induced by placing Sprague Dawley newborn rats in a water bath at 37°C for 19 min. Once their physiological conditions improved, they were given to surrogate mothers that had delivered normally within the last 24 h. The control group was represented by non-fostered vaginally delivered pups, mimicking the clinical situation. Treatment with PEA (10 mg/kg) was administered within the first hour of life. Modifications in the hippocampus were analyzed with conventional electron microscopy, immunohistochemistry (for NeuN, pNF-H/M, MAP-2, and GFAP) and western blot (for pNF H/M, MAP-2, and GFAP). Behavior was also studied throughout Open Field (OF) Test, Passive Avoidance (PA) Task and Elevated Plus Maze (EPM) Test. After 1 month of the PA insult, we observed neuronal nucleus degeneration in CA1 using electron microscopy. Immunohistochemistry revealed a significant increase in pNF-H/M and decrease in MAP-2 in CA1 reactive area. These changes were also observed when analyzing the level of expression of these markers by western blot. Vertical exploration impairments and anxiety-related behaviors were encountered in the OF and EPM tests. PEA treatment attenuated PA-induced hippocampal damage and its corresponding behavioral alterations. These results contribute to the elucidation of PEA neuroprotective role after PA and the future establishment of therapeutic strategies for the developing brain.

show abstract

“…A growing body of evidence suggests that OEA and PEA might also participate in the regulation of reward-related behaviors (Coppola and Mondola 2013;Grosshans et al 2014;Melis et al 2008). For example, habit-forming substances such as alcohol and nicotine may alter OEA and PEA content in brain regions involved in reward (Bilbao et al 2016;Buczynski et al 2013;Melis et al 2008), while exogenous administration of these compounds has been shown to reduce the intake of alcohol and nicotine (Bilbao et al 2016;Melis et al 2008).…”

Section: Introductionmentioning

confidence: 99%

N-acylethanolamine acid amidase (NAAA) inhibition decreases the motivation for alcohol in Marchigian Sardinian alcohol-preferring rats

2020

View full text Add to dashboard Cite

Rationale-N-acylethanolamine acid amidase (NAAA) is an intracellular cysteine hydrolase that terminates the biological actions of oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), two endogenous lipid-derived agonists of the nuclear receptor, peroxisome proliferator-activated receptor-α. OEA and PEA are important regulators of energy balance, pain and inflammation, but recent evidence suggests that they might also contribute to the control of reward-related behaviors.Objectives and Methods-In the present study, we investigated the effects of systemic and intracerebral NAAA inhibition in the two-bottle choice model of voluntary alcohol drinking and on operant alcohol self-administration.Results-Intraperitoneal injections of the systemically active NAAA inhibitor ARN19702 (3 and 10 mg/kg) lowered voluntary alcohol intake in a dose-dependent manner, achieving ≈ 47% reduction at the 10 mg/kg dose (p<0.001). Water, food or saccharin consumption was not affected by the inhibitor. Similarly, ARN19702 dose-dependently attenuated alcohol self-administration under both fixed-ratio 1 (FR-1) and progressive ratio schedules of reinforcement. Furthermore, microinjection of ARN19702 (1, 3 and 10 μg/μl) or of two chemically different NAAA inhibitors, ARN077 and ARN726 (both at 3 and 10 μg/μl), into the midbrain ventral tegmental area produced dose-dependent decreases in alcohol self-administration under FR-1 schedule. Microinjection of ARN19702 into the nucleus accumbens had no such effect.Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. http://www.springer.com/gb/openaccess/authors-rights/aam-terms-v1

show abstract

Palmitoylethanolamide: From endogenous cannabimimetic substance to innovative medicine for the treatment of cannabis dependence

Cited by 9 publications

References 72 publications

Systemic Administration of Oleoylethanolamide Protects from Neuroinflammation and Anhedonia Induced by LPS in Rats

Systemic Administration of Oleoylethanolamide Protects from Neuroinflammation and Anhedonia Induced by LPS in Rats

Palmitoylethanolamide Ameliorates Hippocampal Damage and Behavioral Dysfunction After Perinatal Asphyxia in the Immature Rat Brain

N-acylethanolamine acid amidase (NAAA) inhibition decreases the motivation for alcohol in Marchigian Sardinian alcohol-preferring rats

Contact Info

Product

Resources

About