Name: Erich Antonio Moraes
Type: MSc dissertation
Publication date: 31/08/2015

Namesort ascending Role
Luiz Carlos Schenberg Advisor *

Examining board:

Namesort ascending Role
Vanessa Beijamini Harres Internal Examiner *
Luiz Carlos Schenberg Advisor *
Karla Nívea Sampaio External Examiner *
Jeyce Willig Quintino dos Santos External Alternate *
Alexandre Martins Costa Santos Internal Alternate *

Summary: Panic attacks (PAs) can be precipitated either by the inhalation of 5% carbon dioxide (CO2) or by the infusion of 0.5 mol/L sodium lactate (LAC) in predisposed patients, but not in healthy subjects or patients with other psychiatric disorders. These and other observations suggested that PAs are "suffocation false alarms". The panic disorder is likewise characterized by the high comorbidity with childhood separation anxiety (CSA). Consequently, the CSA has been considered both as a predisposing factor of panic and as an important factor of the resistance to panicolitics. Preclinical studies of our laboratory showed, on the other hand, that panicolitics attenuate experimental panic attacks to both the electrical stimulation of the dorsal periaqueductal gray matter (DPAG) and the intravenous injection of potassium cyanide (KCN) in doses and regimenssimilar to those used in the clinics. These studies also showed that neonatal social isolation, a model of CSA, supress the panicolitic effect of fluoxetine (FLX, 1-2, 21 days) on panic-like responses to electrical stimulation of DPAG. Therefore, the present study evaluated the effects of a higher dose of FLX (Experiment-1) as well as of the infusion of LAC (Experiment-2) on PAs to electrical stimulations of DPAG or to intravenous injections of KCN, respectively, in rats subjected to social isolation as neonates. In Experiment-1, adult male Wistar rats subjected either to 3-h daily neonatal social isolation (NSI) or brief-handling fictive social isolation (FSI) throughout the lactation period, were implanted with electrodes into the DPAG and treated with saline (0.9%, SAL) or fluoxetine (4, FLX4) over 21 days. Although the panic thresholds remained virtually unchanged in SAL-treated FSI rats, they were progressively increased in SAL-treated NSI rats. Moreover, FLX4-treated rats showed higher thresholds that those treated with SAL. However, comparison to baseline thresholds showed that FLX4 had differential effects on FSI and NSI groups, increasing or reducing thresholds, respectively. Although there were no significant differences between ISF and FSI at the end of the treatment with FLX4, the threshold percent changes relative to baseline suggest that FLX4 had effects even facilitatory on panic responses. The resistance of neonatally-isolated rats to FLX4 extended previous studies with smaller doses of FLX. In turn, the results of Experiment-2 showed that intravenous infusion of a clinically effective concentration of LAC (0.5 mol/L) does not have any effect on the escape responses to KCN in rats either virgin or submitted to the FSI or NSI. Although the latter results suggest that panics to both KCN (experimental) and LAC (clinical) are mediated by different systems, conclusions require further experiments with higher concentrations of LAC.

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