The motivation for exercise over palatable food is dictated by cannabinoid type-1 receptors.

The lack of intrinsic motivation to engage in, and adhere to, physical exercise has major health consequences. However, the neurobiological bases of exercise motivation are still unknown. This study aimed at examining whether the endocannabinoid system (ECS) is involved in this process.

Antidepressant and pro-motivational effects of repeated lamotrigine treatment in a rat model of depressive symptoms.

Background: The antiepileptic lamotrigine is approved for maintenance treatment of bipolar disorder and augmentation therapy in treatment-resistant depression. Previous preclinical investigations showed lamotrigine antidepressant-like effects without addressing its possible activity on motivational aspects of anhedonia, a symptom clinically associated with poor treatment response and with blunted mesolimbic dopaminergic responsiveness to salient stimuli in preclinical models. Thus, in rats expressing a depressive-like phenotype we studied whether repeated lamotrigine administration restored behavioral responses to aversive and positive stimuli and the dopaminergic response to sucrose in the nucleus accumbens shell (NAcS), all disrupted by stress exposure.

Aripiprazole relieves motivational anhedonia in rats.

Background: Anhedonia is considered a relevant feature in depression and psychosis, characterized by poor treatment outcome, and associated with deficits in mesolimbic dopaminergic responsiveness. Clinical studies suggest the potential utility of aripiprazole as adjunctive therapy for resistant depression. Since aripiprazole can stabilize the dopaminergic system, in search of tailored therapeutic strategies for reward dysfunctions, we investigated whether the drug restored motivation toward positive stimuli in a rat model.

Fasting biases μ-opioid receptors toward β-arrestin2-dependent signaling in the accumbens shell.

The μ-opioid receptor (MOR) and dopamine D receptor are co-expressed in the medium spiny neurons of striatal areas and the signaling pathways activated by these two receptors are in functional competition. However, in certain conditions an integrated response mediated by the dopamine D receptor transduction system is observed. In mice, morphine administration induces hypermotility and this response has been described in terms of a β-arrestin2-dependent mechanism that favors prevalent dopamine D receptor activation.

PPARα modulation of mesolimbic dopamine transmission rescues depression-related behaviors.

Depressive disorders cause a substantial burden for the individual and the society. Key depressive symptoms can be modeled in animals and enable the development of novel therapeutic interventions. Chronic unavoidable stress disrupts rats' competence to escape noxious stimuli and self-administer sucrose, configuring a depression model characterized by escape deficit and motivational anhedonia associated to impaired dopaminergic responses to sucrose in the nucleus accumbens shell (NAcS).