The neural basis of drug craving: An incentive-sensitization theory of addiction

New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of key signalling molecules involved in this regulatory system highlights its importance to human health. Although each new signalling pathway discovered in the hypothalamus is a potential target for drug development in the treatment of obesity, the growing number of such signalling molecules indicates that food intake is controlled by a highly complex process. To better understand how energy homeostasis can be achieved, we describe a model that delineates the roles of individual hormonal and neuropeptide signalling pathways in the control of food intake and the means by which obesity can arise from inherited or acquired defects in their function.

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Central nervous system control of food intake

Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...

Brown Adipose Tissue: Function and Physiological Significance

https://lsa.umich.edu/psych/research&labs/berridge/publications/Berridge&RobinsonBrResRev1998.pdf

What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?

We hypothesize that there is a general bias, based on both innate predispositions and experience, in animals and humans, to give greater weight to negative entities (e.g., events, objects, personal traits). This is manifested in 4 ways: (a) negative potency (negative entities are stronger than the equivalent positive entities), (b) steeper nega tive gradients (the negativity of negative events grows more rapidly with approach to them in space or time than does the positivity of positive events, (c) negativity domi nance (combinations of negative and positive entities yield evaluations that are more negative than the algebraic sum of individual subjective valences would predict), and (d) negative differentiation (negative entities are more varied, yield more complex conceptual representations, and engage a wider response repertoire). We review evi dence for this taxonomy, with emphasis on negativity dominance, including literary, historical, religious, and cultural sources, as well as the psychological literatures on learning, attention, impression formation, contagion, moral judgment, development, and memory. We then consider a variety of theoretical accounts for negativity bias. We suggest that 1 feature of negative events that make them dominant is that negative entities are more contagious than positive entities.

/pdf/negativity-bias-negativity-dominance-and-contagion-2njh4nr8pi.pdf

Negativity Bias, Negativity Dominance, and Contagion

WITHDRAWN: The effect of peripheral leptin infusions on energy balance in chronically maintained decerebrate rats

Vagal afferent neuron (VAN) signaling sends information from the gut to the brain and is fundamental in the neural control of feeding behavior and metabolism Recent findings reveal that VAN signaling also plays a critical role in cognitive processes, including hippocampus (HPC)-dependent memory VANs, located in nodose ganglia, express receptors for various gut-derived endocrine signals, however, the function of these receptors with regards to feeding behavior, metabolism, and memory control is poorly understood We hypothesized that VAN-mediated processes are influenced by ghrelin, a stomach-derived orexigenic hormone, via communication to its receptor (growth hormone secretagogue receptor [GHSR]) expressed on gut-innervating VANs To examine this hypothesis, rats received nodose ganglia injections of an adeno-associated virus (AAV) expressing short hairpin RNAs targeting GHSR (or a control AAV) for RNA interference-mediated VAN-specific GHSR knockdown Results reveal that VAN GHSR knockdown induced various feeding and metabolic disturbances, including increased meal frequency, impaired glucose tolerance, delayed gastric emptying, and increased body weight compared to controls Additionally, VAN-specific GHSR knockdown impaired HPC-dependent episodic contextual memory and reduced HPC brain-derived neurotrophic factor expression, but did not affect anxiety-like behavior or levels of general activity A functional role for endogenous VAN GHSR signaling was further confirmed by results revealing that VAN signaling is required for the hyperphagic effects of ghrelin administered at dark onset, and that gut-restricted ghrelin-induced increases in VAN firing rate require intact VAN GHSR expression Collective results reveal that VAN GHSR signaling is required for both normal feeding and metabolic function as well as HPC-dependent memory

/pdf/ghrelin-signaling-regulates-feeding-behavior-metabolism-and-2pkdyocdjj.pdf

Ghrelin signaling regulates feeding behavior, metabolism, and memory through the vagus nerve

/pdf/nucleus-of-the-solitary-tract-a2-neurons-control-feeding-3mrcal1o.pdf

Nucleus of the solitary tract A2 neurons control feeding behaviors via projections to the paraventricular hypothalamus

tim bartness died on September 24, 2015 at his home in Atlanta after a year-long battle with multiple myeloma. He was 62 years old. Tim was a superbly innovative and imaginative scientist. Over the course of his distinguished career he applied a broad understanding of metabolic physiology, behavior

Tim Bartness (1953-2015).

Hindbrain growth hormone secretagogue receptor (GHSR) agonism increases food intake, yet the underlying neural mechanisms remain unclear. The functional effects of hindbrain GHSR antagonism by its endogenous antagonist, liver expressed antimicrobial peptide 2 (LEAP2) are also yet unexplored. To test the hypothesis that hindbrain GHSR agonism attenuates the food intake inhibitory effect of gastrointestinal (GI) satiation signals, ghrelin (at a feeding subthreshold dose) was administered to the fourth ventricle (4V) or directly to the nucleus tractus solitarius (NTS) prior to systemic delivery of the GI satiation signal cholecystokinin (CCK). Also examined, was whether hindbrain GHSR agonism attenuated CCK-induced NTS neural activation (c-Fos immunofluorescence). To investigate an alternate hypothesis, that hindbrain GHSR agonism enhances feeding motivation and food-seeking, intake stimulatory ghrelin doses were administered to the 4V and fixed ratio 5 (FR-5), progressive ratio (PR), and operant reinstatement paradigms for palatable food responding were evaluated. Also assessed were 4V LEAP2 delivery on food intake and body weight (BW) and on ghrelin-stimulated feeding. Both 4V and NTS ghrelin blocked the intake inhibitory effect of CCK and 4V ghrelin blocked CCK-induced NTS neural activation. While 4V ghrelin increased low-demand FR-5 responding, it did not increase high-demand PR or reinstatement of operant responding. 4V LEAP2 reduced chow intake and BW and blocked hindbrain ghrelin-stimulated feeding. Data support a role for hindbrain GHSR in bidirectional control of food intake through mechanisms that include interacting with the NTS neural processing of GI satiation signals but not food motivation and food-seeking.

Harvey J. Grill

Papers

WITHDRAWN: The effect of peripheral leptin infusions on energy balance in chronically maintained decerebrate rats

Ghrelin signaling regulates feeding behavior, metabolism, and memory through the vagus nerve

Nucleus of the solitary tract A2 neurons control feeding behaviors via projections to the paraventricular hypothalamus

Tim Bartness (1953-2015).

Hindbrain ghrelin and LEAP2, ligands for GHSR, bidirectionally control food intake.