Phenotyping neurons activated in the mouse brain during restoration of salt debt.

Salt overconsumption contributes to hypertension, which is a major risk factor for stroke, heart and kidney disease. Characterising neuronal pathways that may control salt consumption is therefore important for developing novel approaches for reducing salt overconsumption. Here, we identify neurons within the mouse central amygdala (CeA), lateral parabrachial nucleus (LPBN), intermediate nucleus of the solitary tract (iNTS), and caudal NTS (cNTS) that are activated and display Fos immunoreactivity in mice that have consumed salt in order to restore a salt debt, relative to salt replete and salt depleted controls. Double-label immunohistochemical studies revealed that salt restoring mice had significantly greater densities of activated enkephalin neurons within the CeA and iNTS, while statistically significant changes within the LPBN and cNTS were not observed. Furthermore, within the CeA, restoration of salt debt conferred a significant increase in the density of activated calretinin neurons, while there was no change relative to control groups in the density of activated neurons that co-expressed protein kinase C delta (PKC-δ). Taken together, these studies highlight the importance of opioid systems within the CeA and iNTS in neuronal processes associated with salt restoration, and may aid the development of future pharmacological and other strategies for reducing salt overconsumption.

The influence of opioid dependence on salt consumption and related psychological parameters in mice and humans.

BACKGROUND: The consumption of dietary salt (NaCl) is controlled by neuronal pathways that are modulated by endogenous opioid signalling. The latter is disrupted by chronic use of exogenous opioid receptor agonists, such as morphine. Therefore, opioid dependence may influence salt consumption, which we investigated in two complimentary studies in humans and mice. METHODS: Human study: three groups were recruited: i. Individuals who are currently opioid dependent and receiving opioid substitution treatment (OST); ii. Previously opioid dependent individuals, who are currently abstinent, and; iii. Healthy controls with no history of opioid dependence. Participants tasted solutions containing different salt concentrations and indicated levels of salt 'desire', salt 'liking', and perceptions of 'saltiness'. Mouse study: preference for 0.1 M versus 0.2 M NaCl and overall levels of salt consumption were recorded during and after chronic escalating morphine treatment. RESULTS: Human study: Abstinent participants' 'desire' for and 'liking' of salt was shifted towards more highly concentrated salt solutions relative to control and OST individuals. Mouse study: Mice increased their total salt consumption during morphine treatment relative to vehicle controls, which persisted for 3 days after cessation of treatment. Preference for 'low' versus 'high' concentrations of salt were unchanged. CONCLUSION: These findings suggest a possible common mechanistic cross-sensitization to salt that is present in both mice and humans and builds our understanding of how opioid dependence can influence dietary salt consumption. This research may help inform better strategies to improve the diet and overall wellbeing of the growing number of individuals who develop opioid dependence.