Dysregulation of Striatal Dopamine Signaling by Amphetamine Inhibits Feeding by Hungry Mice

Cannon, Chase A; Abdallah, Luna; Tecott, Laurence H.; During, Matthew J.; Palmiter, Richard D.

doi:10.1016/j.neuron.2004.10.009

Cited by 50 publications

(50 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mice were allowed to acclimate for 3 days before initiating DT treatment and data collection. Body weight and intake of liquid diet were recorded every 24 h. Licking activity at food and water dispensers was monitored continuously by computer as described (24,49). Licking data were processed and grouped into 2-h bins by using the MatLab software (Mathworks).…”

Section: Methodsmentioning

confidence: 99%

Starvation after AgRP neuron ablation is independent of melanocortin signaling

Howell

Cowley

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

106

View full text Add to dashboard Cite

Ablation of inhibitory agouti-related protein (AgRP)-expressing neurons in the arcuate nucleus that also synthesize ␥-aminobutyric acid (GABA) and neuropeptide Y in adult mice leads to starvation within 1 week. The removal of inhibition from the AgRP neurons onto neighboring proopiomelanocortin neurons and their common postsynaptic neurons is predicted to stimulate melanocortin signaling, which is known to inhibit appetite. To examine the importance of uncontrolled melanocortin signaling in mediating starvation in this model, we ablated AgRP neurons in A y /a mice that have chronic blockade of the melanocortin signaling. The blockade of melanocortin signaling did not ameliorate the rate of starvation. On both WT and A y /a genetic backgrounds, there was a progressive decrease in meal frequency after AgRP neuron ablation. Surprisingly, intraoral feeding also was dramatically reduced after the ablation of AgRP neurons. These results indicate that both the appetitive and consummatory aspects of feeding become impaired in a melanocortin-independent manner after AgRP neuron ablation.T he melanocortin signaling pathway in the medial hypothalamus has emerged as a critical mediator of hormonal and neuronal signals that regulate energy balance (1-3). Genetic, pharmacological, anatomical, and electrophysiological techniques have established a pivotal role for proopiomelanocortin (POMC) neurons in the arcuate (ARC) and their signaling via melanocortin (␣-MSH) to cells bearing melanocortin-4 receptors (MC4R) in the paraventricular nucleus (PVN) and other brain regions in the control of appetite and metabolism (1,4,5). Neighboring cells that coexpress neuropeptide Y (NPY) and agouti-related protein (AgRP) also have been implicated in appetite and energy balance because these peptides stimulate robust feeding when injected into the brain, and their mRNA levels increase in the ARC under starvation conditions, as well as in obese animals deficient in leptin signaling (2,(6)(7)(8). Various experiments suggest that NPY acts by inhibiting the activity of POMC neurons and postsynaptic MC4R-bearing cells by activating G␣i-coupled NPY Y1 and/or Y5 receptors (7, 9-12). The activation of these receptors is predicted to counteract melanocortin activation of G␣s-coupled MC4R. AgRP acts in concert with NPY by blocking the binding of ␣-MSH to MC4R (8,13,14). The neurons that make NPY and AgRP also produce GABA, which inhibits POMC neurons and probably MC4R-bearing cells (15,16). Thus, these AgRP neurons are poised to inhibit melanocortin signaling by the neighboring POMC cells.The activation of melanocortin signaling by leptin inhibits appetite while stimulating metabolism (1, 2, 6). Consequently, the inactivation of mouse genes encoding leptin, leptin receptor, POMC, or MC4R leads to obesity (17)(18)(19)(20). However, the inactivation of genes encoding NPY, AgRP, or both has little effect on energy balance (21-23). These genetic results suggest that compensatory mechanisms in the KO mice mask the normal role of these peptides. Nevertheles...

show abstract

Section: Methodsmentioning

confidence: 99%

Starvation after AgRP neuron ablation is independent of melanocortin signaling

Howell

Cowley

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

106

View full text Add to dashboard Cite

show abstract

Section: Neurobiology Of Systems Mediating Caloric Balancementioning

confidence: 99%

“…Other important anorexigenic factors include serotonin (via 5HT 1b , 5HT 2A , and 5HT 2C receptors) and corticotropin-releasing hormone (CRH; Kalra et al, 1999;Makarenko et al, 2002;Muller et al, 2004), whereas orexigenic processes are favored by endogenous opiate peptides (Morley, 1987; Horvath et al, (Kalra et al, 1999). Lastly, basal ganglia dopamine is involved in nonhedonic metabolic drive and goal-directed motor behavior towards procurement of food (Volkow et al, 2002c;Cannon et al, 2004).As a whole, this well-orchestrated machinery is almost infallible in preventing caloric deficit states as it sets of hunger (and supresses satiety), accompanied by negative subjective experiences ranging from slight discomfort to restlessness and food obsession. Eating can therefore be construed as a negative reinforcer as it brings an end to the discomfort induced by hunger (Saper et al, 2002).…”

mentioning

confidence: 99%

“…Other important anorexigenic factors include serotonin (5HT) via 5HT 1b , 5HT 2A and 5HT 2C receptors (Makarenko et al, 2002;Muller et al, 2004) and corticotropin-releasing hormone (CRH; Kalra et al, 1999), whereas orexigenic processes are favored by endogenous opioid peptides (Horvath et al, 1992;Kalra et al, 1999;Morley, 1987) and glucocorticoids (Kalra et al, 1999). Lastly, dopamine in the dorsal striatum (basal ganglia) is involved in nonhedonic homeostatic drive and goal-directed motor behavior towards procurement of food (Cannon et al, 2004;Volkow et al, 2002c). For the clarity of presentation, the scheme was rendered out-of-scale and simplified to reduce the numbers of the displayed links and structures to those of direct relevance to the main themes of this review.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

133

142

View full text Add to dashboard Cite

Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

show abstract

“…The dopamine neurotransmitter functions in reward-motivated behaviors; thus, changes to extracellular dopamine levels can result in a number of diseases (Palmiter, 2007;Yamamoto and Seto, 2014). Low levels of dopamine are associated with attention deficit hyperactivity disorder (ADHD), depression, and under-eating (Cannon et al, 2004;Sotak et al, 2005). Studies in rats showed that upon feeding or drinking, there was a rapid firing of dopamine in the brain.…”

Section: Introductionmentioning

confidence: 99%

Manipulation of components that control feeding behavior in Drosophila melanogaster increases sensitivity to amino acid starvation

Slade¹,

Staveley²

2016

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Feeding is a complex behavior that is regulated by several internal mechanisms. Neuropeptides are able to survey quantities of stored energy and inform the organism if nutrient intake is required. In addition to this homeostatic regulation, a post-feeding reward system positively reinforces feeding. Slight adjustments to either system can tilt the balance to affect the energy reserves and survivorship in times of nutrient adversity. Neuropeptide F (NPF), a homolog of the mammalian neuropeptide Y, acts to induce feeding within the homeostatic regulation of this behavior. Drosophila and other insects bear a shorter form of NPF known as short NPF (sNPF) that can influence feeding. A neural hormone regulator, the dopamine transporter (DAT), works to clear dopamine from the synapses. This action may manipulate the post-feeding reward circuit in that lowered dopamine levels depress feeding, and excess dopamine levels encourage feeding. Here, we have overexpressed and impaired the activities of NPF, sNPF, and DAT in Drosophila, and we examined their ability to survive during conditions of amino acid starvation. Too much or too little NPF or sNPF, which are key players in homeostatic feeding regulation, leads to increased sensitivity to amino acid starvation and diminished survivorship when compared to controls. When DAT, a member of the post-feeding reward system, is either overexpressed or reduced via mutation, Drosophila has increased sensitivity to amino acid starvation. Taken together, these results indicate that subtle variation in the expression of key components of these systems impacts survivorship during adverse nutrient conditions.

show abstract

Dysregulation of Striatal Dopamine Signaling by Amphetamine Inhibits Feeding by Hungry Mice

Abstract: and A substantial literature is consistent with the hypothesis that systemic AMPH reduces appetite by release of Howard Hughes Medical Institute University of Washington catecholamines within the perifornical lateral hypothalamus (pfLH) (Baptista et al., 1993; Chen et al., 2001; Kuo,

Cited by 50 publications

References 119 publications

Starvation after AgRP neuron ablation is independent of melanocortin signaling

Starvation after AgRP neuron ablation is independent of melanocortin signaling

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Manipulation of components that control feeding behavior in Drosophila melanogaster increases sensitivity to amino acid starvation

Contact Info

Product

Resources

About