Link Between Sodium-Craving Genes and Drug Addiction in the Brain

Craving for sodium has been found to be a deliberate instinct, triggered by deficiency and other hormonal signals. As seen from the experiments conducted on mice in conditions of sodium deficiency, the hypothalamic genes (genes related to the part of the brain that lies below the thalamus) for dopamine (a monoamine neurotransmitter formed in the brain) regulation are highly expressed. Correspondingly, administration of antagonists satisfies the craving for sodium. Gene enhancement in hypothalamic genes of sodium-deficient mice showed a parallel enhancement in addiction genes for substances like cocaine and opiates. It was found that within just 10 minutes after salt absorption from the intestine, the salt hunger was nullified. Consequently, this also addresses the addiction problem and this finding proves to be of great significance in the health sector.

The desire to have sodium is due to the following reasons: sodium deficit, stress-induced adrenocorticotropic hormone (ACTH), and reproduction. Hunger for salt is usually accompanied by thirst for water. Drinking saline water at this juncture removes this hunger within 10 minutes after absorption of the salt from the gut. The hypothalamus is associated with genes for instinctive behavior such as those involved in response to sodium appetite. Enrichment of these genes showed increased expression of one or more genes linked to opiate and cocaine addiction. It has been found that administration of salt solution addresses the salt deficiency. The resolution of sodium appetite also concurrently alleviated the addiction issue linked with these genes. Thus, drug intervention to deal with hypothalamus-generated physiological manifestations could help in the elimination of addiction to opiates and cocaine that looms large as a social and medical problem.

* Sodium deficiency was induced in a set of experimental mice by feeding them on a low-sodium diet for seven days.
* Sodium intake was measured for the next three days. Mice were killed and hypothalamic tissue was taken for the study.
* In the control group, the diet of the control mice had 0.5 percent NaCl.
* Gratification was studied by estimation of water consumption and by examination of brain tissue samples, which were taken 10 minutes later.
* After the control experiment, the protocol was repeated. In the post-deprivation period, the mice were injected with saline antagonist.
* Genetic and statistical analyses were carried out to measure the differences in gene expression and concomitant regulation.

Data/Results/Key findings
* Specific hypothalamic genes involved in neuron signal transmission and pathways that decide the fate of substances like dopamine were identified.
* The consumption of salt solution resulted in the loss of control on gene regulation within 10 minutes, which suggested that genes located close to the instinct-regulating gene showed reduced expression.
* The satisfaction of sodium appetite obstructed the regulation of linked genes and hence, the need for reward pathway in sodium appetite was removed. Subsequently, the addiction was satisfied without the actual substance.
* It was found that thirst accompanied the appetite for salt. This was reduced when antagonists to dopamine receptors were given, which indicated that this leads to a compensatory effect on addiction genes.

Next steps/Shortcomings
The general mechanism of gene changes and the related behavioral outcomes have not yet been elucidated. The rate at which gratification reverses the craving, i.e., rate of protein alterations, which addresses the genetic expression, was not calculated. Other physiological aspects of sodium deficiency like blood pressure control were not considered in this study. The neurology behind the gene regulation needs to be understood at the molecular level.

This experiment is pivotal in the understanding of gene regulatory processes related to reward pathways and gratification of craving with specificity to hypothalamic genes. Concerted gene regulation and expression are studied in the context of genes associated with sodium appetite and genes for addiction to cocaine and opiates that are located close to the former. Introduction of antagonists of dopamine and other similar receptors led to the elimination of sodium hunger and also reduced thirst. Thus, the reward pathway that has been known for a long time to medical science seems to offer a solution in terms of damaging instinctive behavior, such as substance abuse. Hence, the results of this study are likely to provide an effective and feasible solution to deal with the medical as well as social implications of addiction.

For More Information:
Relation of Addiction Genes to Hypothalamic Gene Changes Subserving Genesis And Gratification of a Classic Instinct, Sodium Appetite
Publication Journal: PNAS Early Edition, 2011
By Wolfgang Liedtke; Michael McKinley; Duke University, Durham, North Carolina; University of Melbourne, Parkville, Victoria, Australia

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