Age-Dependent Modulation of Glutamatergic Synaptic Transmission by Ethanol in the Prefrontal Cortex

Abstract

Abstract AGE-DEPENDENT MODULATION OF GLUTAMATERGIC SYNAPTIC TRANSMISSION BY ETHANOL IN THE PREFRONTAL CORTEX Terese Andersson 2017 Institute of Neuroscience and Physiology The Sahlgrenska Academy at University of Gothenburg Introduction: Dysregulation of the prefrontal cortex (PFC) is a crucial feature of addiction. Alcohol and nicotine are commonly co-abused and evidence suggests that they interact on the nicotinic acetylcholine receptor (nAChR). Impaired prefrontal function in mice, due to chronic ethanol (EtOH) exposure, have been linked to changes in glutamatergic neurotransmission in the PFC. Aim: The aim of this project was therefore to analyse, at the synaptic level, if differences exist in the PFC of young rats compared with adult regarding glutamatergic neurotransmission – under normal conditions and following treatment with nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (MEC), and/or EtOH. Methods/results: Using electrophysiological recordings in brain slice preparations we analyzed the effects of EtOH treatment on population spike (PS) amplitude in the juvenile rat PFC and found that treatment with 50 mM and 100 mM but not 20 mM EtOH significantly depressed PS amplitude. We also analyzed the effect of treatment with MEC (10 𝜇M), which by 5 itself had no effect on PS amplitude, while the EtOH-induced depression was blocked in slices treated with MEC. Finally, we analyzed the differences between juvenile and adult rat slice preparations in treatment with 50 mM EtOH. There was no significant depression in the adult slice preparations. Conclusions: EtOH depressed PS amplitude in the PFC of juvenile rat slice preparations. Treatment with MEC blocked this depression strongly indicating that it was dependent upon nAChRs, presumably on GABAergic neurons. EtOH induced a significant depression of PFC output in juvenile, but not adult rat slice preparations. Data from the present study further supports the notion that the adolescent brain is more sensitive to the effects of EtOH. Thus underscoring the importance of developing effective preventive interventions in order to postpone alcohol-debut as late as possible.