Induction of a Salt Appetite Alters Dendritic Morphology in Nucleus Accumbens and Sensitizes Rats to Amphetamine

Roitman, Mitchell F.; Na, Elisa S.; Anderson, Gregory J.; Jones, Theresa A.; Bernstein, Ilene L.

doi:10.1523/jneurosci.22-11-j0001.2002

Cited by 99 publications

(103 citation statements)

References 28 publications

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“…Specifically, it was found that furosemide administration increased dendritic branching and spines of neurons within the shell of nucleus accumbens (Roitman et al, 2002). Such changes in morphology are similar to those that occur in the nucleus accumbens after repeated use of amphetamines (Robinson and Kolb 1997).…”

Section: Central Gustatory Processingmentioning

confidence: 73%

Richter and sodium appetite: From adrenalectomy to molecular biology

Krause

Sakai

2007

Appetite

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Nearly three-quarters of a century ago, Curt Richter removed the adrenal glands from rats and noted that the animal's vitality was dependent on its increased consumption of sodium chloride. In doing so, Richter revealed an innate behavioral mechanism that serves to maintain the hydromineral balance of an animal faced with sodium deficit. This experiment and others like it, led to the development of a field of research devoted to the investigation of salt appetite. The following is a discussion of how Richter's initial observations gave birth to an evolving field that incorporates multiple approaches to examine the drive to consume sodium. KeywordsSalt appetite; Angiotensin; Aldosterone; Corticosterone; Richter The Discovery of Salt AppetiteAt the time that Richter began his career at Johns Hopkins University much of the research examining ingestive behavior focused on the responses of individual organs or closely coordinated systems. Richter's pioneering work initiated a fundamental paradigm shift that moved the focus to adaptations of the organism as a whole. Specifically, he was interested in changes in behavior that compensated for perturbations in the internal environment. His approach toward investigation of such behaviors was as thorough as it was fundamental. Richter manipulated diet, interfered with the nervous system, and removed or replaced glandular secretions in attempt to understand the nutritional, neural, and endocrine signals that contribute to behavior.Richter created disturbances in the nutritional or mineral content of the internal environment with dietary deficiency. Subsequently, "self selection" experiments were performed where choices of different minerals and nutrients were presented for consumption. More often than not, animals would consume minerals and nutrients in amounts that would alleviate their experimentally-induced deficiencies. One of the most striking behaviors that Richter observed was that of rats voluntarily ingesting salt when faced with sodium deficit. Sodium chloride was removed from the rats' food and they were given access to water and 3 % NaCl solution. The intake of the NaCl solution was approximately 1% of the total diet, which remarkably, is the

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Section: Central Gustatory Processingmentioning

confidence: 73%

Richter and sodium appetite: From adrenalectomy to molecular biology

Krause

Sakai

2007

Appetite

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“…2D) suggests a possible neural plasticity mechanism, whereby ARC could function to prime lateral hypothalamic orexinergic neurons for subsequent activation of reward circuitry underlying gratification behavior (20). Interestingly, a previous study reported an increase of dendritic processes in the nucleus accumbens shell in sodium deficiency and also, a sensitization of sodium-depleted animals to amphetamine (21). Morphological alterations seem characteristic of ARC effects.…”

Section: Resultsmentioning

confidence: 94%

“…This lock into ancient pathways could constitute a partial explanation for the recalcitrance of drug addiction to therapeutic attempts aimed at abstinence. Animals or human addicts with nonsatisfied primal needs show altered responses to drugs of abuse (21,33).…”

Section: Discussionmentioning

confidence: 99%

Relation of addiction genes to hypothalamic gene changes subserving genesis and gratification of a classic instinct, sodium appetite

Liedtke

McKinley

Walker

et al. 2011

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

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Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked adrenocorticotropic hormone (ACTH), and reproduction. Genome-wide microarrays in sodium-deficient mice or after ACTH infusion showed up-regulation of hypothalamic genes, including dopamine-and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP-32), dopamine receptors-1 and -2, α-2C-adrenoceptor, and striatally enriched protein tyrosine phosphatase (STEP). Both DARPP-32 and neural plasticity regulator activity-regulated cytoskeleton associated protein (ARC) were upregulated in lateral hypothalamic orexinergic neurons by sodium deficiency. Administration of dopamine D1 (SCH23390) and D2 receptor (raclopride) antagonists reduced gratification of sodium appetite triggered by sodium deficiency. SCH23390 was specific, having no effect on osmotic-induced water drinking, whereas raclopride also reduced water intake. D1 receptor KO mice had normal sodium appetite, indicating compensatory regulation. Appetite was insensitive to SCH23390, confirming the absence of off-target effects. Bilateral microinjection of SCH23390 (100 nM in 200 nL) into rats' lateral hypothalamus greatly reduced sodium appetite. Gene set enrichment analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates and cocaine). This finding of concerted gene regulation was attenuated on gratification with perplexingly rapid kinetics of only 10 min, anteceding significant absorption of salt from the gut. Salt appetite and hedonic liking of salt taste have evolved over >100 million y (e.g., being present in Metatheria). Drugs causing pleasure and addiction are comparatively recent and likely reflect usurping of evolutionary ancient systems with high survival value by the gratification of contemporary hedonic indulgences. Our findings outline a molecular logic for instinctive behavior encoded by the brain with possible important translational-medical implications.

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“…Previous research has established that repeated sodium depletions produce a significant increase in sodium appetite as indicated by incremental increases in hypertonic saline solution intake over the first three or four episodes of sodium depletion (Falk, 1966;Falk and Herman, 1961;Leshem et al, 2004;Roitman et al, 2002;Sakai et al, 1987;Sakai et al, 1989). The purpose of the present experiment was to investigate possible neural mechanisms underlying this behavioral plasticity.…”

Section: Discussionmentioning

confidence: 91%

“…Behavioral experiments have demonstrated that animals depleted of sodium multiple times show an enhancement in hypertonic saline ingestion in both acute and chronic tests (Falk, 1966;Leshem et al, 2004;Roitman et al, 2002;Sakai et al, 1987;Sakai et al, 1989). The neurobiological changes responsible for this enhancement are unknown, but it may be attributable to plasticity in sodium appetite-related or reward-related nuclei.…”

Section: Introductionmentioning

confidence: 99%

The neural substrates of enhanced salt appetite after repeated sodium depletions

Morris

Johnson

et al. 2007

Brain Research

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Sodium appetite is associated with a form of behavioral plasticity in which animals experimentally depleted of sodium progressively increase their intake of hypertonic NaCl over several successive (on 2 to 4 occasions) depletion. The present experiment explored the nature of this plasticity by quantifying Fos-immunoreactivity (Fos-ir) in structures implicated in the mediation of sodium appetite and in the signaling of reward. Rats were depleted of sodium with the diuretic furosemide three times (3F), one time (2V1F) or sham depleted (i.e., vehicle treated; 3V). Rats were given sodium appetite tests for the first two treatments. The sodium appetite test was omitted after the third depletion. Fos-ir activity was quantified in the paraventricular nucleus (PVN), subfornical organ (SFO), supraoptic nucleus (SON), nucleus accumbens (NAc) shell and core, basolateral (BLA) and central amygdala (CeA), and medial prefrontal cortex (mPFC). Animals receiving repeated sodium depletions increased sodium ingestion across initial depletions. Fos-ir activity was markedly enhanced in the SFO, BLA, and shell of the NAc of 3F rats relative to 2V1F and 3V animals. These results indicate that repeated experience with sodium depletion and ingestion affect both behavioral and neural responses to sodium. Experience with sodium depletion enhances its ingestion and may have a direct impact on central structures implicated in sodium appetite and reward signaling.

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Induction of a Salt Appetite Alters Dendritic Morphology in Nucleus Accumbens and Sensitizes Rats to Amphetamine

Cited by 99 publications

References 28 publications

Richter and sodium appetite: From adrenalectomy to molecular biology

Richter and sodium appetite: From adrenalectomy to molecular biology

Relation of addiction genes to hypothalamic gene changes subserving genesis and gratification of a classic instinct, sodium appetite

The neural substrates of enhanced salt appetite after repeated sodium depletions

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