Increased Noradrenaline Levels in the Rostral Pons can be Reversed by M1 Antagonist in a Rat Model of Post-traumatic Stress Disorder

Abstract

The dysregulation of hypothalamic-pituitary-adrenal axis and noradrenergic, serotonergic and glutamatergic systems are thought to be involved in the pathophysiology of post-traumatic stress disorder. The effect of selective M1 muscarinic receptor antagonist, pirenzepine on anxiety indices was investigated by using elevated plus maze, following exposure to trauma reminder. Upon receiving the approval of ethics committee, Sprague-Dawley rats were exposed to dirty cat litter (trauma) for 10 min and 1 week later, the rats confronted to a trauma reminder (clean litter). The rats also received intraperitoneal pirenzepine (1 or 2 mg/kg/day) or saline for 8 days. Noradrenaline (NA) concentration in the rostral pons was analyzed by HPLC with electrochemical detection. The anxiety indices of the rats subjected to the trauma reminder were increased when compared to control rats (p < 0.05). Pirenzepine treatment in traumatized rats displayed similar anxiety indices of non-traumatized rats treated with physiological saline. Although freezing time was prolonged with pirenzepine in traumatized groups the change was not found statistically significant. The NA level was 1.5 ± 0.1 pg/mg in non-traumatized rats and increased to 2.4 ± 0.2 pg/mg in traumatized rats. Bonferroni post hoc test revealed that the NA content of the rostral pons of the traumatized rats treated with physiological saline was significantly higher than the content of other groups (p < 0.01). We conclude that NA content in the rostral pons increases in respect to confrontation to a trauma reminder which can be reversed by M1 antagonist pirenzepine indicating the roles of M1 receptors.

The Neurochemical Effects of Prazosin Treatment on Fear Circuitry in a Rat Traumatic Stress Model

“…The first part of our study demonstrates that cat litter scent induced stress and resulted in higher cumulative freezing times and lower number of entries into the open arms of elevated plus maze in the stressed rats without prazosin injections. This finding is in accordance with the findings of the previous studies published from our laboratory [11,21]. On the other hand prazosin injections did not produce any significant difference in the total time spent on the open arms neither due to stress exposure nor due to treatments on the elevated plus maze.…”

“…Stressful stimuli of many types produce marked increases in brain noradrenergic function. In an experimental study performed in rats using predator scent test that serves as an experimental model for PTSD, it was stated that NA levels increase in locus coeruleus (LC) in stressed rats [11]. The brain noradrenergic system is involved in mediating the fear conditioning [12,13].…”

Behavioral effects of Bj-PRO-7a, a proline-rich oligopeptide from Bothrops jararaca venom

“…We used a systemic ( ip ) injection of pirenzepine to maintain the same route of administration for all drugs, which also ensured a minimally invasive method. Although pirenzepine presents low liposolubility, previous studies demonstrated that it crosses the blood brain barrier, reaches the central nervous system (11), and produces central effects (12,13).…”

Altered ratio of proapoptotic and antiapoptotic proteins in different brain regions of female rats in model of post-traumatic stress disorder

“…Our previous another data showed that noradrenaline (NA) content in the rostral pons increased in traumatized rats with cat litter and this increase may serve as an additional neurochemical evidence for the model. Pirenzepine suppressed the anxiety index but it was not that effective in decreasing the prolonged freezing times [18].…”

“…Our previous another data showed that noradrenaline (NA) content in the rostral pons increased in traumatized rats with cat litter and this increase may serve as an additional neurochemical evidence for the model. Pirenzepine suppressed the anxiety index but it was not that effective in decreasing the prolonged freezing times [18].In this current study, we wanted to demonstrate the ratio between proapoptotic and antiapoptotic proteins in the dorsal hippocampus, the amygdaloid complex and the frontal cortex of female rats traumatized with cat litter. The effects of fluoxetine or propranolol on behavioral parameters and neuronal apoptosis were also investigated.…”