Paracetamol - Effect of early exposure on neurotransmission, spatial memory and motor performance in rats.
In the present study we examined the effect of prenatal and early life paracetamol exposure on neurotransmission and its behavioural manifestation in rat male pups. In order to assess the ability of spatial learning and memory consolidation and the level of physical and exploratory activity we conducted a series of behavioural tests: Staircase Test, Hole Board Test and Water Maze. The concentrations of monoamines, metabolites and amino acids were determined using High Performance Liquid Chromatography in the prefrontal cortex, hippocampus and striatum. The effect on spatial memory and exploratory behaviour was most pronounced in animals treated with the lower dose of paracetamol. In this group we have observed a much lower motor activity and decreased head-dipping behaviour. Simultaneously, the number of crossings in the Water Maze under the previous platform position during the probe trial was significantly higher in rats treated with paracetamol at the dose of 5mg/kg. There was also a preference for a new location of a platform to the original position of the platform in the reversal probe trial of this group. These results indicate that early paracetamol exposure produces major changes in serotonergic and dopaminergic neurotransmission in the prefrontal cortex and striatum. At the same time, administration of the drug in early life results in the spectacular change in the amino acid level, in particular in the hippocampus and cortex. This has been reflected in the behaviour of animals in the Water Maze and Hole Board Test (without any noticeable impact on the Staircase Test).
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland.
Kamilla
K
Blecharz-Klin
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland.
Agnieszka
A
Piechal
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland.
Katarzyna
K
Jawna-Zboińska
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland.
Justyna
J
Pyrzanowska
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland.
Adriana
A
Wawer
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland.
Ilona
I
Joniec-Maciejak
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland. Electronic address: etyszkiewicz@wum.edu.pl.
Ewa
E
Widy-Tyszkiewicz
D000082:Acetaminophen / Q000633:toxicity*; D000596:Amino Acids / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D000069077:Memory Consolidation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology* / Q000523:psychology*; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D000596:Amino Acids; D018712:Analgesics, Non-Narcotic; D015306:Biogenic Monoamines; D000082:Acetaminophen
Acetaminophen; Behaviour; Memory; Neurotransmission; Paracetamol; Prenatal