Oleoylethanolamide dose‐dependently attenuates cocaine‐induced behaviours through a PPARα receptor‐independent mechanism

Abstract

Oleoylethanolamide (OEA) is an acylethanolamide that acts as an agonist of nuclear peroxisome proliferator-activated receptor alpha (PPARα) to exert their biological functions, which include the regulation of appetite and metabolism. Increasing evidence also suggests that OEA may participate in the control of reward-related behaviours. However, direct experimental evidence for the role of the OEA-PPARα receptor interaction in drug-mediated behaviours, such as cocaine-induced behavioural phenotypes, is lacking. The present study explored the role of OEA and its receptor PPARα on the psychomotor and rewarding responsiveness to cocaine using behavioural tests indicative of core components of addiction. We found that acute administration of OEA (1, 5 or 20 mg/kg, i.p.) reduced spontaneous locomotor activity and attenuated psychomotor activation induced by cocaine (20 mg/kg) in C57Bl/6 mice. However, PPARα receptor knockout mice showed normal sensitization, although OEA was capable of reducing behavioural sensitization with fewer efficacies. Furthermore, conditioned place preference and reinstatement to cocaine were intact in these mice. Our results indicate that PPARα receptor does not play a critical, if any, role in mediating short- and long-term psychomotor and rewarding responsiveness to cocaine. However, further research is needed for the identification of the targets of OEA for its inhibitory action on cocaine-mediated responses.

Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

“…This interpretation arises because beta-adrenergic activation stimulates synthesis of OEA in response to cold exposure in adipocytes and to satiety in the small intestine (LoVerme et al, 2006; Fu et al, 2011). Moreover, OEA has been recently proposed to control cocaine-associated behaviors (Bilbao et al, 2013). Concerning the CB2 receptor, although we have not measured its expression in the present study, we cannot rule out a role for this receptor in the neuroadaptive responses to cocaine, as recently suggested (Xi et al, 2011; Aracil-Fernandez et al, 2012).…”

Involvement of norepinephrine and serotonin system in antidepressant-like effects of oleoylethanolamide in the mice models of behavior despair

“…1) is an endocannabinoid analogy that belongs to a family of endogenous acylethanolamides [2]. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of reward-related behaviors [1,8]. Systemic administration of OEA to rats results in elevated OEA plasma levels, as has also been reported in patients with post-traumatic stress disorder [9].…”

“…Depression is caused by many psychological, social, environmental, and genetic factors [1], and has increasingly plagued people in modern life [2]. Current antidepressant drugs can only alleviate some symptoms of depression, and side effects are common.…”

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats

“…Although, it is well known that locomotor activity in rodents reaches its peak during the dark phase of the light/dark cycle (Benstaali et al, ), we carried out the cocaine sensitization protocol during the light phase since we previously found robust cocaine‐sensitized locomotor responses during this phase of the cycle (Bilbao et al, ; Blanco et al, ,b; Luque‐Rojas et al, ). In addition, melatonin seems to have suppressive effects on cocaine sensitization (Uz et al, ).…”