As most of you well know, the neurotransmitter dopamine and its receptors are critical to the brain’s reward pathways, and dysfunction of these pathways is associated with addictive behaviors. This paper recently published in the journal Nature Neuroscience elucidates the role of dopamine receptors in compulsive eating with obesity. The authors first noticed that…

“…development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking.”

On investigating the underlying mechanism they found that compulsive feeding was present in obese but not lean rats because…

“Striatal (corpus striatum of the brain) dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs.”

What did they conclude from their data?

“These data demonstrate that overconsumption of palatable food [which produces insulin resistance] triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.”

A paper published in the Journal of Neuroendocrinology adds further support to the importance of dopamine in appetite regulation. Ghrelin is a peptide produced in the stomach that increases appetite by stimulating a part of the brain (VTA = ventral tegmental area) that is rich in dopamine producing neurons:

“Interestingly, ghrelin infusions into the VTA increase food intake dramatically, and stimulate dopamine release from the VTA…ghrelin increases food intake by modulating the activity of dopaminergic neurones in the VTA.“

The author offers this conclusion:

“On the basis of these data as well as the fact that VTA dopamine cells respond to other metabolic hormones such as insulin and leptin, it is proposed that VTA dopamine cells…are first-order sensory neurones that regulate appetitive behaviour…”

Blood sugar and insulin have such a powerful effect on the brain and energy (nutrient) seeking behavior it’s no wonder there’s abundant evidence that they are associated with dopamine in the regulation of appetite. This paper published in Pharmacology Biochemistry and Behavior notes that:

“The hormones insulin, leptin, and ghrelin have been demonstrated to act in the central nervous system (CNS) as regulators of energy homeostasis…CNS circuitry that subserves reward and is also a direct and indirect target for the action of these endocrine regulators of energy homeostasis.”

Their research demonstrates that insulin and leptin can dampen reward satisfaction through an effect on dopamine signaling:

“Specifically, insulin and leptin can decrease food reward behaviors and modulate the function of neurotransmitter systems and neural circuitry that mediate food reward, the midbrain dopamine (DA) and opioidergic pathways.”

Another study published in Acta Diabetologica also confirms the profound effect of insulin on dopamine signaling:

“Administration of various doses of glucose to rats produced a significant decrease of dopamine turnover…a close connection between 3,4-dihydroxyphenylacetic acid (DOPAC) (metabolite of dopamine) variation and insulin plasma level was demonstrated. However, glucose did not affect dopamine metabolism in starved or streptozotocin-treated rats (rats made to be diabetic). This indicates that the effect of glucose on the central dopaminergic system is mediated by pancreatic insulin, even in the presence of endogenous brain insulin.”

Moreover, dopamine gives the message that the cells are satisfied and shuts down pancreatic production of insulin as described in this paper published in The Journal of Biological Chemistry:

“Both dopamine and insulin actions in the brain modulate appetite and feeding behaviors. In this work we show for the first time that pancreatic beta cells express dopamine receptors mediating inhibition of glucose-stimulated insulin secretion.”

They go on to further describe the close association of dopamine with insulin and problems related to blood sugar regulation and obesity:

“Moreover, antipsychotic (neuroleptic) drugs blocking dopamine receptors may cause hyperinsulinemia, hypoglycemia, increase appetite, and obesity and are associated with diabetes. Therefore, dopamine action on beta cells (of the pancreas that secrete insulin)might have relevant implications for the study of obesity and diabetes, in particular in situations where dopamine transmission is altered.”

As if that wasn’t enough, the effect of insulin on dopamine signaling is so strong that it can even block the effects of amphetamine as described in this study published in PLoS Biology:

“Amphetamines mediate their behavioral effects by stimulating dopaminergic signaling throughout reward circuits of the brain. This property of amphetamine relies on its actions at the dopamine transporter (DAT)…we and others have revealed the novel ability of insulin signaling pathways in the brain to regulate DAT function as well as the…actions of amphetamine…by depleting insulin, or…insulin signaling, we can severely attenuate amphetamine-induced dopamine release and impair DAT function. Our findings demonstrate in vivo the novel ability of insulin signaling to dynamically influence the neuronal effects of amphetamine-like psychostimulants.”

The bottom line: compulsive eating (and other addictive behaviors) occurs when the reward (satisfaction) circuits are not functioning. To feel satisfied, we need adequate dopamine production and healthy insulin regulation. For the former we have natural precursor therapy to replenish exhausted dopamine resources. Healthy insulin and blood sugar regulation is, of course, a fundamental to any health strategy.