Hippocampal brain amines in methotrexate-induced learning and memory deficit

Sampath Madhyastha, S. N. Somayaji, M. S. Rao, K. Nalini, K. Laxminarayana Bairy

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.

Original languageEnglish
Pages (from-to)1076-1084
Number of pages9
JournalCanadian Journal of Physiology and Pharmacology
Volume80
Issue number11
DOIs
Publication statusPublished - 2002

Fingerprint

Memory Disorders
Methotrexate
Amines
Learning
Brain
Hippocampus
Serotonin
Seizures
Leukoencephalopathies
Injections
Hydroxyindoleacetic Acid
Anti-Anxiety Agents
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Dementia
Wistar Rats
Dopamine
Norepinephrine
Leukemia
High Pressure Liquid Chromatography
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology

Cite this

Madhyastha, S., Somayaji, S. N., Rao, M. S., Nalini, K., & Bairy, K. L. (2002). Hippocampal brain amines in methotrexate-induced learning and memory deficit. Canadian Journal of Physiology and Pharmacology, 80(11), 1076-1084. https://doi.org/10.1139/y02-135
Madhyastha, Sampath ; Somayaji, S. N. ; Rao, M. S. ; Nalini, K. ; Bairy, K. Laxminarayana. / Hippocampal brain amines in methotrexate-induced learning and memory deficit. In: Canadian Journal of Physiology and Pharmacology. 2002 ; Vol. 80, No. 11. pp. 1076-1084.
@article{94ec2019e4e24a92a9ed7c273c1ec40e,
title = "Hippocampal brain amines in methotrexate-induced learning and memory deficit",
abstract = "Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.",
author = "Sampath Madhyastha and Somayaji, {S. N.} and Rao, {M. S.} and K. Nalini and Bairy, {K. Laxminarayana}",
year = "2002",
doi = "10.1139/y02-135",
language = "English",
volume = "80",
pages = "1076--1084",
journal = "Canadian Journal of Physiology and Pharmacology",
issn = "0008-4212",
publisher = "National Research Council of Canada",
number = "11",

}

Madhyastha, S, Somayaji, SN, Rao, MS, Nalini, K & Bairy, KL 2002, 'Hippocampal brain amines in methotrexate-induced learning and memory deficit', Canadian Journal of Physiology and Pharmacology, vol. 80, no. 11, pp. 1076-1084. https://doi.org/10.1139/y02-135

Hippocampal brain amines in methotrexate-induced learning and memory deficit. / Madhyastha, Sampath; Somayaji, S. N.; Rao, M. S.; Nalini, K.; Bairy, K. Laxminarayana.

In: Canadian Journal of Physiology and Pharmacology, Vol. 80, No. 11, 2002, p. 1076-1084.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hippocampal brain amines in methotrexate-induced learning and memory deficit

AU - Madhyastha, Sampath

AU - Somayaji, S. N.

AU - Rao, M. S.

AU - Nalini, K.

AU - Bairy, K. Laxminarayana

PY - 2002

Y1 - 2002

N2 - Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.

AB - Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.

UR - http://www.scopus.com/inward/record.url?scp=0036904348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036904348&partnerID=8YFLogxK

U2 - 10.1139/y02-135

DO - 10.1139/y02-135

M3 - Article

VL - 80

SP - 1076

EP - 1084

JO - Canadian Journal of Physiology and Pharmacology

JF - Canadian Journal of Physiology and Pharmacology

SN - 0008-4212

IS - 11

ER -