Long-Term Abstinence and Relapse: A Novel Role for Hippocampal Activin Signaling

Dietz
This grant will investigate the role of activin signaling in the brain’s hippocampus (HPC) in cue-induced cocaine seeking following both acute and prolonged drug abstinence.

Drug addiction is a chronic brain disease characterized by compulsive use of drugs despite negative consequences. Risk of relapse remains elevated even after long periods of abstinence due to drug-associated cues that provoke drug craving and seeking. Currently, there are no effective pharmacotherapeutic interventions for addiction to stimulants, such as cocaine, highlighting the urgent need for further understanding of the neurobiology of addiction. In an animal addiction model of persistent relapse vulnerability, extended- access cocaine self-administration leads to an abstinent-dependent intensification of cue-induced cocaine craving, a phenomenon that has also been observed in human addicts. While the reward circuitry of the brain is known to play an important role in the drug-dependent plasticity that underlies the addiction disease, the hippocampus (HPC), a crucial member of the circuitry, has not been examined in the progression and maintenance of intensified cue-induced cocaine seeking. This research will elucidate a novel mechanism by which chronic cocaine exposure induces long-term adaptations in the HPC and will provide new direction for the development of novel therapies for cocaine addiction.

Principal Investigator
David Dietz, PhD
Department of Pharmacology and Toxicology

Funding Agency
National Institute on Drug Abuse (NIDA)

Grant Number
R21-DA044486

Dates
2017-2019