A growing body of evidence indicates that environmental information can be transmitted from parents to progeny. Thus, epigenetic changes in the mammalian germline can act as transgenerational carriers 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 the effects of paternal cocaine taking on memory formation in offspring using a rat model of cocaine addiction. We found that 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 will ameliorate learning and synaptic plasticity deficits caused by paternal cocaine taking.
In Specific Aim 2, we will evaluate basal synaptic function, NMDA receptor signaling and epigenetic processes 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.
Mounting evidence suggests that environmental factors in adults can have a substantial impact on their offspring. Recent estimates indicated that there are over 23 million illicit drug users in the United State and at least 5 million children lived wih a father that met the criteria for substance abuse in the past year. Psychostimulants, are the third most abused drug after marijuana and pain killers. One of the most debilitating consequences of cocaine addiction is the cognitive deficits that often accompany chronic drug use. However, it remains unclear whether cocaine-related cognitive impairments in adults are carried into future generations. This proposal will examine whether paternal cocaine taking in an animal model of addiction has deleterious consequences on neurocognition in progeny by combining behavioral, molecular and electrophysiological approaches. Unveiling the mechanisms underlying cocaine-related learning deficits may identify biomarkers associated with cocaine addiction as well as define novel targets for therapeutic development.
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| Wimmer, M E; Briand, L A; Fant, B et al. (2017) Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny. Mol Psychiatry 22:1641-1650 |
