Alcoholism, clinical and experimental research · 2016
Neonatal Ethanol Exposure Impairs Trace Fear Conditioning and Alters NMDA Receptor Subunit Expression in Adult Male and Female Rats.
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Goodfellow Molly J, Abdulla Khalid A, Lindquist Derick H
Аннотация
BACKGROUND: Ethanol (EtOH) exposure in neonate rats during a period comparable to the human third trimester, postnatal days (PD) 4 to 9, leads to persistent deficits in forebrain-dependent cognitive function--modeling the dysfunction seen in individuals diagnosed with fetal alcohol spectrum disorders. EtOH-exposed adult rats are impaired in auditory trace fear conditioning (TFC), a form of Pavlovian conditioning in which a neutral conditioned stimulus (CS; tone) is followed by an aversive unconditioned stimulus (US; footshock), with both stimuli separated in time by a stimulus-free "trace" interval (TI). TFC acquisition depends on N-methyl-d-aspartate NMDA receptor (NMDAR) activation in the dorsal hippocampus (DH), ventral hippocampus (VH), and medial prefrontal cortex (mPFC).
METHODS: Male and female rat pups were sham-intubated (SI) or intragastrically intubated with EtOH (5E; 5 g/kg/d) over PD 4 to 9 and, as adults, submitted to TFC with a 15-second tone CS and 30-second TI. Whole-cell tissue lysates from the DH, VH, and mPFC of TFC rats and DH synaptic/extrasynaptic membrane fractions from experimentally naïve animals were analyzed via Western blot for NMDAR subunit (GluN1, GluN2A, GluN2B) expression.
RESULTS: Freezing behavior during CS-alone test trials was significantly reduced in both male and female 5E rats, relative to same-sex controls. Western blot results based on DH tissue samples revealed a greater proportion of GluN2A to GluN2B subunits in 5E rats, relative to SI rats, and significantly reduced synaptic GluN2B and PSD-95 expression.
CONCLUSIONS: EtOH-induced changes in DH NMDAR subunit expression-particularly synaptic GluN2B, which is critical for TFC-are proposed to weaken long-term memory consolidation and, during behavioral testing, diminish CS-evoked freezing behavior.
METHODS: Male and female rat pups were sham-intubated (SI) or intragastrically intubated with EtOH (5E; 5 g/kg/d) over PD 4 to 9 and, as adults, submitted to TFC with a 15-second tone CS and 30-second TI. Whole-cell tissue lysates from the DH, VH, and mPFC of TFC rats and DH synaptic/extrasynaptic membrane fractions from experimentally naïve animals were analyzed via Western blot for NMDAR subunit (GluN1, GluN2A, GluN2B) expression.
RESULTS: Freezing behavior during CS-alone test trials was significantly reduced in both male and female 5E rats, relative to same-sex controls. Western blot results based on DH tissue samples revealed a greater proportion of GluN2A to GluN2B subunits in 5E rats, relative to SI rats, and significantly reduced synaptic GluN2B and PSD-95 expression.
CONCLUSIONS: EtOH-induced changes in DH NMDAR subunit expression-particularly synaptic GluN2B, which is critical for TFC-are proposed to weaken long-term memory consolidation and, during behavioral testing, diminish CS-evoked freezing behavior.