Recent studies have shown that the neuropeptides arginine-8-vasopressi
n (AVP) and oxytocin (OXT) are released within the supraoptic (SON) an
d paraventricular (PVN) nuclei of the hypothalamus in response to micr
odialysis of these nuclei with high-NaCl perfusion media. These result
s suggest an inherent osmosensitivity of SON and PVN neurons. To inves
tigate whether the observed release of AVP/OXT is a unique phenomenon
to these neuropeptides, several brain regions were examined for the re
lease of amino acids or dopamine in response to high- or low-NaCl stim
ulation. Urethane-anesthetized male Sprague-Dawley rats were perfused
with five-ion solution using O-shaped microdialysis probes. Samples we
re collected at 30-min intervals and analyzed for amino acids and dopa
mine by HPLC. In the dialysates of all perfusion areas, including the
SON, PVN, hippocampus, and striatum, concentrations of Asp, Glu, Ser,
Gin, Gly, taurine (Tau), and gamma-aminobutyric acid (GABA) were signi
ficantly increased during perfusion with high-NaCl medium. This releas
e was found to be dose dependent when tested in the hippocampus and st
riatum with perfusion medium containing 0.5 or 1./0 M NaCl. However, o
nly the release of Glu and Ser was found to be Ca2+ dependent. In cont
rast, the use of mannitol, a nonionic osmolyte, for perfusions in the
striatum in concentrations of 0.5 and 1 M resulted in reduced levels o
f amino acids in the dialysates (Glu, Ser, Gin, and Tau). Low-NaCl per
fusion medium (0.01 M) resulted insignificantly increased Glu, Tau, G
ly, and GABA levels in the striatum. In addition, dopamine levels in s
triatal dialysates were significantly increased during stimulation wit
h 1 M NaCl. These results indicate that stimulation with high NaCl con
centrations affects the release of several neurotransmitters and is no
t specific for AVP and OXT. The described phenomenon of the release of
amino acids in response to this stimulation seems to be a response to
the changed ionic concentration rather than to the osmolality. In lig
ht of these findings shown for amino acids and dopamine as well as tho
se previously reported for AVP, OXT, and angiotensin, iti would appear
that sensitivity to tonicity changes brought about by microdialysis m
ay be a feature of many transmitter systems.