Leptin increases striatal dopamine D2 receptor binding in leptin‐deficient obese (ob/ob) mice

Abstract

Peripheral and central leptin administration has been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R binding differences contribute to the phenotypic behaviors of leptin deficient ob/ob mice and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Striatal basal D2R binding (measured with autoradiography [ 3 H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice leptin decreased striatal D2R binding whereas in ob/ob mice leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2 receptor expression in striatum and that these effects are genotype/phenotype dependent.

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary

“…That is to say, it is the brain's response to the environment, more so that the environment itself, that dictates the full metabolic outcome of environmental changes such as the presentation of the westernized diet. The neurophysiological literature is now replete with studies demonstrating the important roles of several neural circuits that impact peripheral fuel metabolism (reviewed in [32]) including hypothalamic arcuate-alpha melanocortin-stimulating hormone (αMSH) [33][34][35] and arcuate neuropeptide Y (NPY) -paraventricular nuclei (PVN) circuits [36][37][38], the lateral hypothalamic (LH) leptinorexin mesolimbic circuit [39][40][41][42], ventromedial hypothalamic and arcuate leptin autonomic/neuroendocrine circuits [43][44][45][46][47], and the insulin arcuate [48] and dopamine mesolimbic circuits [49,50] to name just a few. Emerging experimental evidence suggests important roles for the biological clock system residing within and around the SCN of the hypothalamus in the integration of these CNS circuits to create an orchestrated organized CNS output signal (program) to the peripheral organs respecting fuel metabolism (see discussion below) [51][52][53][54].…”

“…It has been postulated that decreased dopaminergic signaling within the mesolimbic system allows for overfeeding and glucose intolerance in the absence of a sufficient reward signal [116][117][118][119][120][121]. Moreover, leptin activation of dopaminergic neurons within the mesolimbic system is believed to account in part for its actions to maintain body weight and normal insulin sensitivity, and this leptin effect on dopamine function is diminished in obesity [41,47,122]. Although not well recognized, dopamine acts within the arcuate hypothalamus to stimulate proopiomelanocortin (POMC) -α-MSH synthesis, a major contributor to feeding inhibition and insulin sensitivity (reviewed in [52]).…”

Neurobiology of food addiction

“…More research is also needed to better understand the degree to which salt, sugar, and fat act synergistically to motivate hedonic eating. Investigations into the gut-brain interactions [31] and hormone-dopamine [32] addictive properties of other types of ingredients -particularly those found in processed or energy-dense foods -are warranted as well.…”

Clinicotherapeutic Potential of Leptin in Alzheimer’s Disease and Parkinson’s Disease

“…Various studies have mainly focused on leptin effects on the mesolimbic dopamine function and feeding behavior [63][64][65]. A strong association between plasma leptin and cerebrospinal fluid (CSF) dopamine levels ( = 0.74; < 0.01) in humans has been shown in one study [66].…”

“…Leptin receptors are present in dopaminergic neurons in midbrain [67,68] and leptin acts directly on these neurons [63]. Leptin has been shown to modulate D2 receptor expression in striatum, and a unique interaction between the leptin receptors and D2 receptors exists in these neurons in mice [64]. Although these results indicate a potential role of leptin in regulating the action of dopamine in the brain, the exact molecular mechanisms of such actions of leptin are yet to be elucidated.…”