Paracetamol—The outcome on neurotransmission and spatial learning in rats

Blecharz-Klin, Kamilla; Piechal, Agnieszka; Pyrzanowska, Justyna; Joniec-Maciejak, Ilona; Kiliszek, Przemyslaw; Widy-Tyszkiewicz, Ewa

doi:10.1016/j.bbr.2013.07.008

Cited by 26 publications

(22 citation statements)

References 53 publications

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“…These results are consistent with the earlier data showing the 14 modulation of serotonergic and noradrenergic neurotransmission in the prefrontal cortex, hypothalamus and striatum after long-term administration of paracetamol in adult rats (Blecharz-Klin et al, 2013). Our findings are also consistent with the results of Courade and co-workers (2001) who found the increased levels of serotonin in the hypothalamus, posterior cortex, striatum, hippocampus and brain stem but not in the spinal cord.The equilibrium loss of serotonin in the medulla oblongata may affect the higher functions of the CNS.…”

Section: Discussionsupporting

confidence: 96%

Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata

Blecharz-Klin¹,

Joniec-Maciejak²,

Jawna³

et al. 2015

Environmental Toxicology and Pharmacology

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Section: Discussionsupporting

confidence: 96%

Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata

Blecharz-Klin¹,

Joniec-Maciejak²,

Jawna³

et al. 2015

Environmental Toxicology and Pharmacology

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“…Very high doses of APAP have shown impaired memory performance in animals12, probably linked to endogenous COX-2 inhibition, with a sex-dependent effect of COX-2 inhibition on spatial memory13,32 and a more impaired spatial retention in female mice 32. While APAP effect appears deleterious at high doses, normal/low doses of APAP do enhance spatial memory and performance possibly via the central serotonergic system and increased release of endogenous monoamines (serotonin and noradrenaline) in the brain 33,34. The endocannabinoid system also plays a role in spatial memory and in attention, cognition, and mood, via CB1Rs localized to noradrenergic axon terminals, with norepinephrine release, and stimulation of the α2A receptor that improves the attention/cognition performance 35–37.…”

Section: Discussionmentioning

confidence: 99%

Paracetamol sharpens reflection and spatial memory: a double-blind randomized controlled study in healthy volunteers

Pickering¹,

Macian²,

Dubray³

et al. 2016

DDDT

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BackgroundAcetaminophen (APAP, paracetamol) mechanism for analgesic and antipyretic outcomes has been largely addressed, but APAP action on cognitive function has not been studied in humans. Animal studies have suggested an improved cognitive performance but the link with analgesic and antipyretic modes of action is incomplete. This study aims at exploring cognitive tests in healthy volunteers in the context of antinociception and temperature regulation. A double-blind randomized controlled study (NCT01390467) was carried out from May 30, 2011 to July 12, 2011.MethodsForty healthy volunteers were included and analyzed. Nociceptive thresholds, core temperature (body temperature), and a battery of cognitive tests were recorded before and after oral APAP (2 g) or placebo: Information sampling task for predecisional processing, Stockings of Cambridge for spatial memory, reaction time, delayed matching of sample, and pattern recognition memory tests. Analysis of variance for repeated measures adapted to crossover design was performed and a two-tailed type I error was fixed at 5%.ResultsAPAP improved information sampling task (diminution of the number of errors, latency to open boxes, and increased number of opened boxes; all P<0.05). Spatial planning and working memory initial thinking time were decreased (P=0.04). All other tests were not modified by APAP. APAP had an antinociceptive effect (P<0.01) and body temperature did not change.ConclusionThis study shows for the first time that APAP sharpens decision making and planning strategy in healthy volunteers and that cognitive performance and antinociception are independent of APAP effect on thermogenesis. We suggest that cognitive performance mirrors the analgesic rather than thermic cascade of events, with possibly a central role for serotonergic and cannabinoid systems that need to be explored further in the context of pain and cognition.

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“…However, paracetamol concentration has not been significant statistical difference from kidney and brain in several rat studies [16,17]. Also, Blecharz Klin et al [19] have been showed that therapeutic doses of paracetamol cause significant changes in neurotransmission with subtle changes concerning behavior and particularly spatial learning in rat brain structures. Although Hendrickson and Bizovi [18] indicated that paracetamol affected the central nervous system (CNS) by consuming glutathione, but they could not explained how the CNS is affected by acute paracetamol poisoning in their prestudy.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effects of Erdosteine and N-acetyl Cysteine in Rats With Paracetamol Induced Hippocampal Tissue Damage

Bahadir¹

2014

J Phys Chem Biophys

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Paracetamol—The outcome on neurotransmission and spatial learning in rats

Cited by 26 publications

References 53 publications

Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata

Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata

Paracetamol sharpens reflection and spatial memory: a double-blind randomized controlled study in healthy volunteers

The Protective Effects of Erdosteine and N-acetyl Cysteine in Rats With Paracetamol Induced Hippocampal Tissue Damage

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