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

Well-being : the foundations of hedonic psychology

As humans, we perceive feelings from our bodies that relate our state of well-being, our energy and stress levels, our mood and disposition. How do we have these feelings? What neural processes do they represent? Recent functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body. This system constitutes a representation of 'the material me', and might provide a foundation for subjective feelings, emotion and self-awareness.

How do you feel? Interoception: the sense of the physiological condition of the body.

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?

The activity of single taste neurons was recorded from the nucleus of the solitary tract before (n = 41) and after (n = 58) awake, behaving rats were switched to a sodium-free diet. During sodium deprivation, the spontaneous activity of the neurons increased (142%), but responses to water and sapid stimuli decreased. For all neurons in the sample, the mean response to water decreased to 72% of its predeprivation level, NaCl dropped to 53%, sucrose to 41%, citric acid to 68%, and quinine HCl to 84%. Despite the drop in magnitude, the response profiles of the taste neurons were not changed by the dietary condition. In the Na-replete state, 61% of the activity elicited by NaCl occurred in NaCl-best cells and 33% in sucrose-best neurons. In the depleted state, these values were 60 and 26%, respectively. Nevertheless, at the highest concentrations tested, deprivation did alter the relative responsiveness of the gustatory neurons to sucrose and NaCl in specific categories of neurons. Compared with acute preparations, dietary sodium deprivation in awake, behaving rats produced a more general reduction in the gustatory responses of neurons in the nucleus of the solitary tract. The largest reductions in elicited activity occurred for the "best stimulus" of a particular neuron, thus leading to smaller differences in response magnitude across stimuli, particularly at the highest concentrations tested.

Sodium-deficient diet reduces gustatory activity in the nucleus of the solitary tract of behaving rats.

1. A variety of chemicals that humans describe as sweet drive neurons in the nucleus of the solitary tract (NST) of the rat more vigorously when applied to the taste receptors associated with the nasoincisor ducts (NID) than when applied to taste receptors on the anterior tongue (AT). 2. The differential effects of sweet stimuli applied to the AT and NID also are evident in the set of across-neuron correlations produced by these stimuli. The psychophysical similarity among the sweet stimuli is better accounted for by responses to stimulation of the NID than by responses to stimulation of the AT (mean correlation between pairs of sweet stimuli = +0.70 for the NID, +0.44 for the AT). 3. Disaccharides or polysaccharides of glucose, i.e., maltose (0.3 M) and Polycose (0.1 M), are poor stimuli on the NID, evoking responses only 17.8 and 26.7% as great as the response elicited by sucrose (0.3 M), an optimal stimulus for this receptor subpopulation. This suggests that Polycose and maltose interact with receptor sites distinct from those with an affinity for sweet stimuli. Polycose and maltose also are ineffective stimuli on the AT, evoking responses only 11.8 and 4.9% as large as the response evoked by an optimal stimulus for this receptor subpopulation, a mixture of electrolytes (0.3 M NaCl, 0.03 M HCl, and 0.01 M quinine HCl). 4. The relative effectiveness of the sweet sugars in driving NST neurons (sucrose greater than fructose greater than glucose) correlates with their order of effectiveness in generating preference behavior in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Coding the sweet taste in the nucleus of the solitary tract: differential roles for anterior tongue and nasoincisor duct gustatory receptors in the rat.

Substantial behavioral evidence implicates visceral afferent activity in the regulation of feeding behavior. One mechanism often suggested for this influence involves visceral afferent activity interacting with oral or gustatory afferent activity. This brief review summarizes the anatomical and electrophysiological evidence that indicates that such interactions might in fact take place. The available evidence for interactions between visceral and gustatory afferent messages is far from convincing, but perhaps only because the issue has seldom been addressed. The most direct tests suggested by the hypothesis advanced remain to be carried out.

Afferent interactions of cranial nerves involved in ingestion

Rats suppress intake of a normally preferred 0.15% saccharin conditioned stimulus (CS) when it is paired with an aversive agent like lithium chloride (LiCl) or a preferred substances such as sucrose or a drug of abuse. The reward comparison hypothesis suggests that rats avoid intake of a saccharin cue following pairings with a drug of abuse because the rats are anticipating the availability of the rewarding properties of the drug. The present study used bilateral ibotenic acid lesions to examine the role of the gustatory cortex in the suppression of CS intake induced by cocaine, morphine, and LiCl. The results show that bilateral lesions of the insular gustatory cortex (1) fully prevent the suppressive effects of both a 15- and a 30-mg/kg dose of morphine, (2) attenuate the suppressive effect of a 10 mg/kg dose of cocaine, but (3) are overridden by a 20 mg/kg dose of the drug. Finally, these same cortical lesions had no impact on LiCl-induced conditioned taste aversion. The current data show that the insular taste cortex plays an integral role in drug-induced avoidance of a gustatory CS.

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Gustatory insular cortex lesions disrupt drug-induced, but not lithium chloride-induced, suppression of conditioned stimulus intake.

Rats with either electrolytic (Experiment 1) or excitotoxic lesions (Experiment 2) that had been electrophysiologically centered in the gustatory zone of the parabrachial nuclei (PBN) were tested for sucrose and NaCl taste detection thresholds in a conditioned avoidance task. With 1 exception, all of these rats had previously shown severe deficits in acquiring an LiCl-based conditioned taste aversion (CTA) to sucrose, NaCl, or alanine. The rats with excitotoxic lesions also had failed to express a depletion-induced sodium appetite. Despite the uniformity of these deficits, the rats with lesions exhibited varied performance in the detectability task. Roughly 1/3 of the rats did not perform competently, 1/3 had elevated thresholds, and 1/3 showed no or only marginal impairments in taste detectability. These findings demonstrate that the elimination of CTA following PBN lesions is not necessarily linked to an impairment in taste signal detection. Thus, PBN-induced deficits on 1 taste-related task do not entirely correspond with impairments on another.

Ralph Norgren

Papers

Sodium-deficient diet reduces gustatory activity in the nucleus of the solitary tract of behaving rats.

Coding the sweet taste in the nucleus of the solitary tract: differential roles for anterior tongue and nasoincisor duct gustatory receptors in the rat.

Afferent interactions of cranial nerves involved in ingestion

Gustatory insular cortex lesions disrupt drug-induced, but not lithium chloride-induced, suppression of conditioned stimulus intake.

Gustatory detection thresholds after parabrachial nuclei lesions in rats.