title: Involvement of mesolimbic structures in short-term sodium depletion: in situ hybridization and ligand-binding analyses.
abstract: Acute treatment with the diuretic furosemide (Lasix) produces a reduction in plasma Na(+) and volume as well as increased thirst and salt appetite. The resulting hypovolemia stimulates the well-known counter-regulatory physiological response from the renin-angiotensin-aldosterone system. However, the neurochemical players underpinning the behavioral responses of thirst and salt appetite are less clear. Previously, we have reported that salt-replete deoxycorticosterone (DOCA) treatment activates mesolimbic structures associated with reward and goal-seeking behavior. The present study was designed to test whether the same brain regions are affected in a salt-depleted state. In experiment 1, two groups of adult male Sprague-Dawley (SD) rats were injected with Lasix (10 mg/rat, s.c.) and 18 h later were allowed access either to 2% NaCl solution ('Lasix+salt') or only to tap water ('Lasixnosalt') for 2 h. For comparison purposes, a third group received an isotonic saline injection instead of Lasix and was allowed access to the 2% salt solution (Vehicle). All groups were permitted 24 h access to tap water. We found no differences in dynorphin-mRNA levels in any striatal and accumbal regions among any of the treatment groups. However, as found previously in DOCA-treated rats, there were increased enkephalin (ENK)-mRNA and decreased dopamine transporter (DAT) binding levels throughout the striatum in Lasix+salt and decreased ENK-mRNA in Lasixnosalt rats versus Vehicle. In experiment 2, the involvement of the ENKergic and/or dopaminergic system was tested in rats divided into the same three groups described in experiment 1. However, before access to salt or water, the Lasix+salt and the vehicle groups were administered either a delta-opioid, naltrindole or a dopamine D(2) antagonist, raclopride. Only the naltrindole-treated rats showed a blunted intake of salt solution. Thus, these findings along with our neurochemical results suggest that mesolimbic enkephalin might impact salt intake through dopaminergic systems.
authors.affiliation: Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10021, USA. lucasl@rockefeller.edu
authors.forename: Louis R
authors.initials: LR
authors.lastname: Lucas
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Grillo
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
mesh_terms: D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000378:metabolism; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004231:Diuresis; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D004326:Drinking; D004399:Dynorphins / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology*; D017403:In Situ Hybridization; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage; D017673:Sodium Chloride, Dietary / Q000378:metabolism; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D013894:Thirst; D014867:Water / Q000008:administration & dosage
chemical_list: D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D004745:Enkephalins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009292:Narcotic Antagonists; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493216:Slc6a3 protein, rat; D017673:Sodium Chloride, Dietary; D012982:Sodium, Dietary; D014867:Water; D003900:Desoxycorticosterone; D020891:Raclopride; D012965:Sodium Chloride; D009271:Naltrexone; D004399:Dynorphins; D005665:Furosemide; C055382:naltrindole