Name: RUBIA DE SOUZA ARMINI
Publication date: 14/06/2024
Examining board:
Name |
Role |
|---|---|
| AILTON SPIACCI JÚNIOR | Examinador Externo |
| CRISTIAN SETUBAL BERNAB | Examinador Externo |
| FERNANDO ZANELA DA SILVA AREAS | Examinador Interno |
| HÉLIO ZANGROSSI JÚNIO | Examinador Externo |
Summary: Panic disorder is a psychiatric syndrome characterized by the
occurrence of repeated and unexpected panic attacks (PA). Convincing evidence
suggests that the dorsal periaqueductal gray (DPAG) is the substrate of panics both
"respiratory" (similar to fear of suffocation) and "non-respiratory" (similar to fear of
imminent threat). Notably, the hypothalamic-pituitary-adrenal (HPA) axis remains
inactive during PA either spontaneous or induced by administrations of sodium lactate
or CO2. The HPA axis is also inactive in animal models of PA (PAG stimulation, 22-
kHz predator alarm). In chronically stressed rats, quiescence of the HHA axis to a novel
stressor appears to be mediated by cholecystokinergic projections from the PAG to the
paraventricular nucleus of the thalamus (PVT). This mechanism may also be
responsible for the active inhibition of the HHA axis in APs. Therefore, the first study
investigated whether PVT lesions disinhibit the HHA axis during AP ta DPAG
stimulation. The effects of PVT lesions were also evaluated in several behavioral tests.
The results showed that in addition to a small but significant inhibition of the
exophthalmus, trot, and gallop responses to DPAG stimulation, PVT lesions produced
a marked increase in basal corticosterone levels (P<0.001) and a small reduction
(P<0.05) in the corticotrophin response. Although the increase in basal corticosterone
suggests that the PVT exerts a tonic inhibition of HPA axis in non-stressed animals,
this effect compromised the demonstration of active inhibition of the HHA axis during
experimental panic. On the other hand, previous studies have shown that stimulation
of carotid chemoreceptors by potassium cyanide (KCN, i.v.) produces escape
responses that are facilitated by hypercapnia (HPC) and suppressed by lesions of
DPAG. Escape from PAG stimulation was also facilitated by simultaneous infusion of
an extremely low dose of KCN. Surprisingly, however, escape was inhibited by HPC.
It was also unclear whether the KCN model of "pharmacological" hypoxia (HPX) was
equivalent to environmental HPX (hypoxic hypoxia) in which tissue O2 levels are
reduced. Therefore, the second study examined the effects of environmental HPC
(16% CO2), HPX (5% O2), and asphyxia (AFX, 5% CO2 + 5% O2) on the escape
response ta PAG stimulation. The results showed that the PAG harbors an HPX sensor
that is independent of tissue CO2 levels.
