Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults

In pre-adolescence, repeated anesthesia may be required for therapeutic interventions. Adult cognitive and neurobehavioral problems may result from preadolescent exposure to anesthetics. This study examined the long-term morphological and functional effects of repeated sub-anesthetic doses of ketami...

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Main Authors: Amir Barzegar Behrooz, Mahdieh Nasiri, Soheila Adeli, Maryam Jafarian, Seyed Khalil Pestehei, Javad Fahanik Babaei
Format: Article
Language:English
Published: Elsevier 2024-06-01
Series:IBRO Neuroscience Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S266724212400006X
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author Amir Barzegar Behrooz
Mahdieh Nasiri
Soheila Adeli
Maryam Jafarian
Seyed Khalil Pestehei
Javad Fahanik Babaei
author_facet Amir Barzegar Behrooz
Mahdieh Nasiri
Soheila Adeli
Maryam Jafarian
Seyed Khalil Pestehei
Javad Fahanik Babaei
author_sort Amir Barzegar Behrooz
collection DOAJ
description In pre-adolescence, repeated anesthesia may be required for therapeutic interventions. Adult cognitive and neurobehavioral problems may result from preadolescent exposure to anesthetics. This study examined the long-term morphological and functional effects of repeated sub-anesthetic doses of ketamine exposure on male and female rat adults during pre-adolescence. Weaned 48 pre-adolescent rats from eight mothers and were randomly divided into four equal groups: control group and the ketamine group of males and females (20 mg/kg daily for 14 days); then animals received care for 20–30 days. Repeated exposure to sub-anesthetic doses of ketamine on cognitive functions was assayed using Social discrimination and novel object tests. Besides, an elevated plus maze and fear conditioning apparatus were utilized to determine exploratory and anxiety-like behavior in adults. Toluidine blue stain was used to evaluate the number of dead neurons in the hippocampus, and the effects of ketamine on synaptic plasticity were compared in the perforant pathway of the CA1 of the hippocampus. Our study indicates that repeated exposure to sub-anesthetic doses of ketamine during pre-adolescence can result in neurobehavioral impairment in male and female rat adulthood but does not affect anxiety-like behavior. We found a significant quantifiable increase in dark neurons. Recorded electrophysiologically, repeat sub-anesthetic doses of ketamine resulted in hampering long-term potentiation and pair pulse in male adult animals. Our results showed that repeated exposure to sub-anesthetic doses of ketamine during pre-adolescence can induce hippocampus and neuroplasticity changes later in adulthood. This study opens up a new line of inquiry into potential adverse outcomes of repeated anesthesia exposure in pre-adolescent rats.
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spelling doaj.art-c9210ad26c5f4c89abe0f00872e4efa92024-06-14T05:46:38ZengElsevierIBRO Neuroscience Reports2667-24212024-06-0116211223Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adultsAmir Barzegar Behrooz0Mahdieh Nasiri1Soheila Adeli2Maryam Jafarian3Seyed Khalil Pestehei4Javad Fahanik Babaei5Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, IranElectrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, IranElectrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, IranBrain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, IranDepartment of Anesthesiology, Tehran University of Medical Sciences, Tehran, Iran; Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Correspondence to: Neuroscience Research Center Institute, Tehran University of Medical Sciences, Tehran, Iran.Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Correspondence to: Electrophysiology Research Center, Neuroscience Research Center Institute, Tehran University of Medical Sciences, Tehran, Iran.In pre-adolescence, repeated anesthesia may be required for therapeutic interventions. Adult cognitive and neurobehavioral problems may result from preadolescent exposure to anesthetics. This study examined the long-term morphological and functional effects of repeated sub-anesthetic doses of ketamine exposure on male and female rat adults during pre-adolescence. Weaned 48 pre-adolescent rats from eight mothers and were randomly divided into four equal groups: control group and the ketamine group of males and females (20 mg/kg daily for 14 days); then animals received care for 20–30 days. Repeated exposure to sub-anesthetic doses of ketamine on cognitive functions was assayed using Social discrimination and novel object tests. Besides, an elevated plus maze and fear conditioning apparatus were utilized to determine exploratory and anxiety-like behavior in adults. Toluidine blue stain was used to evaluate the number of dead neurons in the hippocampus, and the effects of ketamine on synaptic plasticity were compared in the perforant pathway of the CA1 of the hippocampus. Our study indicates that repeated exposure to sub-anesthetic doses of ketamine during pre-adolescence can result in neurobehavioral impairment in male and female rat adulthood but does not affect anxiety-like behavior. We found a significant quantifiable increase in dark neurons. Recorded electrophysiologically, repeat sub-anesthetic doses of ketamine resulted in hampering long-term potentiation and pair pulse in male adult animals. Our results showed that repeated exposure to sub-anesthetic doses of ketamine during pre-adolescence can induce hippocampus and neuroplasticity changes later in adulthood. This study opens up a new line of inquiry into potential adverse outcomes of repeated anesthesia exposure in pre-adolescent rats.http://www.sciencedirect.com/science/article/pii/S266724212400006XKetamineSub-anesthesiaPre-adolescenceCognitive ProblemsLong-term potentialSex differences
spellingShingle Amir Barzegar Behrooz
Mahdieh Nasiri
Soheila Adeli
Maryam Jafarian
Seyed Khalil Pestehei
Javad Fahanik Babaei
Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults
IBRO Neuroscience Reports
Ketamine
Sub-anesthesia
Pre-adolescence
Cognitive Problems
Long-term potential
Sex differences
title Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults
title_full Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults
title_fullStr Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults
title_full_unstemmed Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults
title_short Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults
title_sort pre adolescence repeat exposure to sub anesthetic doses of ketamine induces long lasting behaviors and cognition impairment in male and female rat adults
topic Ketamine
Sub-anesthesia
Pre-adolescence
Cognitive Problems
Long-term potential
Sex differences
url http://www.sciencedirect.com/science/article/pii/S266724212400006X
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