Mechanisms Underlying Learning Deficits Caused by Paternal Cocaine Taking

Temple Univ Of The Commonwealth, Philadelphia PA

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Abstract

? DESCRIPTION (provided by applicant): A growing body of evidence indicates that environmental information can be inherited. Thus, epigenetic changes in the mammalian germline can act as a transgenerational carrier of environmental perturbations. Cocaine addiction remains a significant health problem in the United States and chronic cocaine use is associated with neurocognitive deficits. However, it remains unclear whether cocaine abuse in parents translates to reduced cognitive function in their offspring. This proposal will focus on th effects of paternal cocaine taking on memory formation in offspring using a rat model of cocaine addiction. We found that the offspring and grand-offspring of cocaine-exposed fathers (sires) have spatial learning deficits and impaired hippocampal synaptic plasticity. In Specific Aim 1, we hypothesize that increasing NMDA receptor signaling in the hippocampus will ameliorate synaptic plasticity and learning deficits caused by paternal cocaine taking. In Specific Aim 2, we will investigate basal synaptic function and NMDA receptor signaling in the hippocampus of the descendants of cocaine-exposed sires. Taken together, this proposal will attempt to illuminate the mechanisms underlying learning deficits that are caused by paternal cocaine taking.