Neonatal NMDA blockade alters the LTP, LTD and cognitive functions in male and female Wistar rats.
Nastaran Golitabari, Forouzan Mohammadian, Ali-Akbar Salari, Mohammad Amani
Neuropharmacology March 1, 2022 DOI: 10.1016/j.neuropharm.2021.108896 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male and female Wistar rats treated in the neonatal period and tested in adulthood |
| Intervention | Phencyclidine (PCP) |
| Dose | 10 mg/kg |
| Duration | PCP administered on postnatal days 7, 9, and 11; behavioral and electrophysiology tests in adulthood |
| Topics | Neuroplasticity |
| Keywords | Learning and memory Nmda blockade Neonatal |
| Key findings | Neonatal phencyclidine treatment in rats significantly reduced paired-pulse facilitation and attenuated long-term potentiation and long-term depression in hippocampal CA1 neurons, with pronounced changes in complex response profile, while leaving basic synaptic transmission largely intact. These electrophysiological changes were comparable in males and females and were associated with impaired spatial reference and working memory in adulthood. |
Abstract
There is compelling evidence that neonatal blockade of NMDA receptors by phencyclidine (PCP) is associated with cognitive impairment in adulthood but little is known about the effects of early life PCP treatment on synaptic function later in life. Here, we sought to determine whether early life exposure to PCP alters the electrophysiologic function of hippocampal CA1 neurons in adult rats. To this end, male and female Wistar rats received either saline or PCP (10 mg/kg) on postnatal days (PND) 7, 9, and 11, and then underwent separate behavioral and electrophysiology tests in adulthood. Neonatal PCP treatment did not alter basic synaptic transmission and had only a modest effect on frequency following (FF) capacity but significantly decreased the paired-pulse facilitation (PPF) in the Schaffer collateral (SC)-CA1 pathway. We found that PCP treatment significantly attenuated the long-term potentiation (LTP) and long-term depression (LTD) in CA1 neurons accompanied by pronounced alteration in complex response profile in adult rats. The electrophysiology data were comparable in male and female rats and reliably associated with impaired spatial reference and working memories in these animals. Overall, this study suggests that blockade of NMDA receptors during early life deteriorates the short-term and long-term synaptic plasticity and complex response profile of CA1 neurons in adulthood.
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Citations in the library
Cites 7
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Differences between adolescents and adults in the acute effects of PCP and ketamine and in sensitization following intermittent administration. Pharmacology, Biochemistry, and Behavior June 1, 2017
- Down-Regulation of Hippocampal Genes Regulating Dopaminergic, GABAergic, and Glutamatergic Function Following Combined Neonatal Phencyclidine and Post-Weaning Social Isolation of Rats as a Neurodevelopmental Model for Schizophrenia. The International Journal of Neuropsychopharmacology November 2016
- Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and activation in later life. European Neuropsychopharmacology May 2012
- Baseline temperature in an animal model of schizophrenia: long-term effects of perinatal phencyclidine administration. Physiology & Behavior February 27, 2008
and 2 more in the library