Mecanismos gabaérgicos e opióides do núcleo parabraquial lateral envolvidos no controle da ingestão de sódio
Abstract
The lateral parabrachial nucleus (LPBN) is a pontine structure located in the
dorsal portion of the cerebelar superior peduncle. LPBN receives afferent projections
from the area postrema (AP) and the medial portion of the nucleus of tractus
solitarius (mNTS) and connects to prosencephalic areas related to hidroelectrolytic
control, such as specific nuclei of the hypothalamus and amygdala. So, an important
role of the LPBN could be integrating ascending information from AP and mNTS that
could affect the activity of prosencephalic areas involved in the hidroelectrolytic
control. Previous studies showed the presence of serotonergic, cholecystokininergic
and α2-adrenergic mechanisms in the LPBN to control water and sodium intake. The
γ-aminobutiric acid (GABA) is an inhibitory neurotransmitter present in the whole
central nervous system and binding to two subtypes of receptors: GABAA and GABAB
receptors. Previously, it was shown the participation of gabaergic mechanisms to
control water, sodium and food intake. Gabaergic activation into the LPBN using
bilateral injections of muscimol (GABAA receptor agonist) and baclofen (GABAB
receptor agonist) induced a strong ingestion of sodium chloride (NaCl 0.3 M) in a
short period of time (3 h) in satiated and normovolemic rats. Besides the presence of
gabaergic mechanisms into the LPBN, it was already shown the presence of opioid
receptors into the LPBN and the involvement of opioid mechanisms in the control of
ingestive behavior. Therefore, the goals of this thesis were:
a) to investigate the participation of GABAA and GABAB receptors on NaCl and water
intake induced by gabaergic activation in the LPBN in satiated and sodium depleted
rats;
b) to study the effects of gabaergic activation into the LPBN on c-fos protein
expression in satiated and sodium depleted rats, with or without access to NaCl 0.3
M;
c) to test if acute lesion of the commissural NTS (cNTS area with the greatest c-fos
protein expression in satiated rats not allowed to drink sodium or water and treated
with muscimol and baclofen into the LPBN) and anteroventral 3o ventricle region
(AV3V an important area involved in the hidroelectrolytic control) could affect the
natriorexigenic and water intake induced by gabaergic activation into the LPBN in
satiated rats;
Abstract
d) to study the effects of inhibition of α2-adrenergic and opioid mechanisms and
activation of serotonergic mechanisms into the LPBN on NaCl and water intakeinduced
by gabaergic activation in the same area in satiated rats;
e) to investigate the participation of opioid mechanisms in the LPBN on sodium and
water intake in satiated and sodium depleted rats;
f) to verify the effects of gabaergic activation in the LPBN on arterial pressure and
urinary excretion.
Male Holtzman or Sprague Dawley rats with bilateral stainless steel guidecannulas
implanted into the LPBN (volume of injection: 0.2 µl) were used. Other
groups of rats, besides the cannulas implanted into the LPBN, they were also
submitted to electrolytic lesion in the cNTS or AV3V region.
In satiated rats, bilateral injections of muscimol (0.5 nmol) and baclofen (0.5
nmol) into the LPBN induced 0.3 M NaCl intake followed by an increase in water
intake. The effects on sodium and water intake produced by muscimol injected into
the LPBN were reduced by previous treatment with bicuculline (GABAA receptor
antagonist - 1.6 nmol), but not CGP 35348 (GABAB receptor antagonist - 50 nmol).
Pre treatment with bicuculline or CGP 35348 into the LPBN abolished the effects of
baclofen on sodium and water intake. In 24 h sodium depleted rats (treatment with sc
furosemide + sodium deficient diet and water for 24 h), muscimol and baclofen
bilaterally injected into the LPBN, produced an early inhibition and a late facilitation of
0.3 M NaCl. Bicuculline, but not CGP 35348, abolished the inhibitory and facilitatory
effects of muscimol injected into LPBN on sodium intake. In relation to sodium
depleted rats treated with baclofen into the LPBN, CGP 35348 abolished the
inhibitory effect, while bicuculline abolished the facilitatory effect of baclofen on
sodium intake. These results suggest that the natriorexigenic effect in satiated rats
and the dual effects on sodium intake in sodium depleted rats produced by muscimol
injected into the LPBN depend on GABAA receptors activation. In relation to baclofen,
in satiated rats the natriorexigenic effect of baclofen depends on activation of GABAA
and GABAB receptors, but in sodium depleted rats, the early inhibition of sodium
intake depends on GABAB receptors activation while the late facilitation depends on
activation of GABAA receptors.
Interestingly, although gabaergic activation promotes a facilitation of sodium
intake, maybe there is not tonic gabaergic participation on sodium depletion-induced
sodium intake, since inhibition of GABAA (bicuculline) and GABAB (CGP 35348)
Abstract
receptors into the LPBN did not affect 0.3 M NaCl and water intake in sodium
depleted rats. Otherwise, in rats trained to drink 0.3 M NaCl only 2 h per day, CGP
35348, but not bicuculline, injected into the LPBN reduced 0.3 M NaCl, suggesting a
tonic participation of GABAB, but not GABAA, receptors on sodium intake control in
the protocol studied. (...)