The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside metabolic regulation. There is a growing interest in repurposing Glucagon-like peptide 1 receptor agonists (GLP-1RAs) as therapeutics for motivation and reward-related behavioural disturbances. Herein, we aim to systematically review the extant evidence on the potential effects of GLP-1RAs on the reward system. The study followed PRISMA guidelines using databases such as OVID, PubMed, Scopus, and Google Scholar. The search focused on "Reward Behavior" and "Glucagon Like Peptide 1 Receptor Agonists" and was restricted to human studies. Quality assessment achieved by the NIH's Quality Assessment of Controlled Intervention Studies RESULTS: GLP-1RAs consistently reduced energy intake and influenced reward-related behaviour. These agents have been associated with decreased neurocortical activation in response to higher rewards and food cues, particularly high-calorie foods, and lowered caloric intake and hunger levels. GLP-1RAs show promise in addressing reward dysfunction linked to food stimuli, obesity, and T2DM. They normalize insulin resistance, and might also modulate dopaminergic signalling and reduce anhedonia. Their effects on glycemic variability and cravings suggest potential applications in addiction disorders.

Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine’s role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression.

The distribution of insulin receptors throughout the brain implicates insulin in physiological functions and disease states, including cognition, appetite, mood, and metabolic disorders. Intranasally administered insulin offers a non-invasive approach for isolating and investigating brain insulin action. This systematic review synthesized the effects of acute intranasal insulin on neuroimaging, cognitive, and behavioural outcomes reported in 48 studies in adults. Age, sex, body mass index, and insulin resistance were found to moderate brain insulin action. Neuroimaging studies showed insulin affects brain activity, cerebral blood flow, and functional connectivity in regions like the hypothalamus, amygdala, and insula. Insulin also modified cognitive function, eating behaviour, and the stress response. Nonetheless, inconsistencies in study designs, dosages, and outcome measures necessitate standardized methodologies to better understand central insulin action. Taken together, insulin's ability to modify stress and fear, appetite and eating behaviour, and cognitive function in both healthy and diseased individuals highlight its potential in the therapeutic and mechanistic exploration of highly prevalent psychiatric, metabolic, and cognitive conditions like mood disorders, obesity, and Alzheimer's disease.