Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

Abstract

Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p.) or vehicle (2% Tween 80). Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

Sodium benzoate induces neurobehavioral deficits and brain oxido‐inflammatory stress in male Wistar rats: Ameliorative role of ascorbic acid

“…[ 64 ] Increased breakdown of acetylcholine leads to downregulation of ACh receptors with consequent undesirable effects on cognitive function. [ 65 ] AChE has also noncholinergic functions such as neurite outgrowth, cell growth, and death. [ 66 ] Increased AChE activity is toxic on neuronal and glia‐like cells in vitro.…”

Neuroprotective Effects of Virgin Coconut Oil Supplemented Diet against Sodium Benzoate-induced Acetylcholinesterase Dysfunction and Cognitive Impairment: Role of Nrf2/NfKb Signaling Pathway

“…Acetylcholine is a neurotransmitter in the brain that plays important role in behavior, learning, and memory functions (Schmatz et al, 2009). Increased acetylcholine breakdown causes acetylcholine receptor downregulation, which has negative consequences on cognitive function (Teodorak et al, 2015). Enhanced AchE activity has been linked to programmed cell death in-vivo and in-vitro (Zhang and Greenberg, 2012).…”

Short post‐weaning social isolation induces long‐term changes in the dopaminergic system and increases susceptibility to psychostimulants in female rats

“…A challenge with an AMPH would induce increased dopaminergic activity and, therefore, increased ROS production due to dopamine metabolism (Teodorak et al, 2015). In this study, after the DEP challenge, despite an overall increased production of ROS (see scale in the figures), animals exposed to social isolation early in life presented an increased production of ROS (F[1,29] = 10.18, p = 0.003) compared to the other groups, while exposure to HSD decreased this parameter (F [1,29] = 8.87, p = 0.006) (Fig.…”

“…This enhanced dopaminergic activity increases locomotor behavior in rats (Garcia‐Mijares et al, 2009; Trainor, 2011). After being released, DA is metabolized enzymatically or through autoxidation, resulting in production of reactive oxygen species (ROS) (Klegeris et al, 1995) and, which may induce an increase in antioxidant enzymes activity (Teodorak et al, 2015).…”