Salt appetite in salt-replete rats: Involvement of mesolimbic structures in deoxycorticosterone-induced salt craving behavior

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 persi sts in rats even with elevated plasma Na+ levels. Since there is evidence t hat the pathways normally associated with salt and water homeostasis are re latively unaffected in the DOCA-treated rat, we hypothesized that other reg ulatory systems may be hyperactive giving rise to this dysfunctional condit ion. The mesolimbic dopaminergic system has long been associated with orien ting and reward-seeking behaviors such as those observed in reproduction, d rug abuse, and appetite. Furthermore, we have previously shown that chronic DOCA administration results in an increase in mRNA levels of the endogenou s opiate enkephalin in male rats given 24-hour access to tap water and 2% N aCl (two-bottle choice). Thus, in the present study, we tested the hypothes is that the mesolimbic dopaminergic system is dysfunctionally sensitized to the presence of a salt stimulus in DOCA-treated animals. Four groups of ra ts were injected with DOCA (5 mg/rat/day, 11 days) and one with vehicle (al l were given access to water but access to salt was regulated). Two DOCA gr oups were given 2 h of 2% NaCl access/day and on the last day, one group wa s 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). Consisten t with our hypothesis, in the shell of the nucleus accumbens (AcbSh) we fou nd relatively higher enkephalin- and tachykinin-mRNA abundance in the 2h vs . 2hX and dynorphin-mRNA in the 24h vs. 24hX groups. In addition, there wer e decreases in dopamine transporter binding in the AcbSh and decreases in t yrosine hydroxylase immunoreactivity throughout the striatum in the 24h vs. 24hX group. Furthermore, rats denied access to salt (2hX and 24hX) had hig her cholecystokinin-mRNA levels in the ventral tegmental area compared to t he 2h and 24h groups, respectively. These results suggest that basal gangli a structures associated with reward and goal-seeking behavior may be activa ted to elicit salt craving behavior in the DOCA-induced salt-appetitive rat . Copyright (C) 2000 S. Karger AG, Basel.