Salt Appetite in Salt-Replete Rats: Involvement of Mesolimbic Structures in Deoxycorticosterone-Induced Salt Craving Behavior

Abstract

Chronic administration of the mineralocorticoid deoxycorticosterone acetate (DOCA) induces a steady and robust increase in salt appetite and plasma Na⁺ over the course of treatment. Interestingly, salt appetite behavior persists in rats even with elevated plasma Na⁺ levels. Since there is evidence that the pathways normally associated with salt and water homeostasis are relatively unaffected in the DOCA-treated rat, we hypothesized that other regulatory systems may be hyperactive giving rise to this dysfunctional condition. The mesolimbic dopaminergic system has long been associated with orienting and reward-seeking behaviors such as those observed in reproduction, drug abuse, and appetite. Furthermore, we have previously shown that chronic DOCA administration results in an increase in mRNA levels of the endogenous opiate enkephalin in male rats given 24-hour access to tap water and 2% NaCl (two-bottle choice). Thus, in the present study, we tested the hypothesis that the mesolimbic dopaminergic system is dysfunctionally sensitized to the presence of a salt stimulus in DOCA-treated animals. Four groups of rats were injected with DOCA (5 mg/rat/day, 11 days) and one with vehicle (all were given access to water but access to salt was regulated). Two DOCA groups were given 2 h of 2% NaCl access/day and on the last day, one group was not given access (2hX). One of the two remaining DOCA groups was given 24-hour access to salt (24h) and the other no access at all (24hX). Consistent with our hypothesis, in the shell of the nucleus accumbens (AcbSh) we found relatively higher enkephalin- and tachykinin-mRNA abundance in the 2h vs. 2hX and dynorphin-mRNA in the 24h vs. 24hX groups. In addition, there were decreases in dopamine transporter binding in the AcbSh and decreases in tyrosine hydroxylase immunoreactivity throughout the striatum in the 24h vs. 24hX group. Furthermore, rats denied access to salt (2hX and 24hX) had higher cholecystokinin-mRNA levels in the ventral tegmental area compared to the 2h and 24h groups, respectively. These results suggest that basal ganglia structures associated with reward and goal-seeking behavior may be activated to elicit salt craving behavior in the DOCA-induced salt-appetitive rat.