Current Research Projects

Identifying mechanisms to disrupt drug-associated memories

Drugs of abuse produce long-lasting neuroplasticity in circuits controlling learning and memory. Many hypothesize that in substance users, drugs exert powerful control over behavior because the memories about the drug, particularly cues associated with use, are stronger than other non-drug memories.  Therefore, it may be possible to treat addiction and prevent relapse by weakening drug-associated memories to make them less potent drivers of behavior. Thus, the lab has identified circuits that encode drug-associated memories in a rat model and determined that these pathways are weakened after extinction of those memories or disruption of reconsolidation. We have used phosphoproteomics to identify novel signaling pathways that regulate the strength of drug-associated memories and have been able to optogenetically induce LTD in the circuits underlying these memories to reduce relapse-like behavior. We are actively trying to identify translatable methods for selectively disrupting drug-associated memories while leaving other memories intact using a combination of in vivo and ex vivo electrophysiology, in vivo calcium imaging, optogenetics, chemogenetics, and synaptic tracing.

Determining interactions between sleep and alcohol use

Chronic alcohol use and abstinence deteriorates sleep quality, whereas sleep disruptions in general may promote the development of alcohol use disorders as people use alcohol as a sleep aid. One great challenge to break this cycle is to obtain mechanistic understanding of how the two-way interactions develop, and to identify targets for effective interventions in order to help reduce alcohol use and to protect individuals from the negative health consequences of chronic sleep disturbances. In collaboration with Dr. Yanhua Huang, we are focusing on how alcohol drinking specifically alters REM sleep and determining if these negative effects are mediated through changes in the excitability of neurons in the medial and lateral habenula. The project uses a combination of EEG/EMG recordings during chronic alcohol drinking in rats, slice electrophysiology of the habenula, chemogenetics, and REM sleep manipulations to determine if REM sleep specific mechanisms can be targeted to improve treatment of alcohol use disorders.

Determining the how alterations in sleep and circadian rhythms in adolescence affects impulsive behavior and propensity to self-administer nicotine and THC

This project is part of a funded NIDA P50, the “Center for Adolescent Reward, Rhythms, and Sleeps (CARRS). The goal of this project is to understand how normal alterations in circadian rhythms and sleep that occur in adolescence affect impulsivity and propensity to acquire nicotine or THC self-administration. Adolescence is characterized by a normal shift in rhythms toward later sleep timing, but this natural tendency is in conflict with typical school start times, often leading to perpetual circadian misalignment and reduced sleep. The Center as a whole will investigate how altered rhythms and sleep affect reward system activity and behavior in both rodent and human adolescents. Our specific project will use fiber photometry in rats to determine how changes in neural activity and dopamine signaling in the PFC and nucleus accumbens of rats are altered by circadian misalignment and sleep loss in adolescents. We will further determine how these manipulations alter impulsivity on the 5-choice serial reaction time task and self-administration of drugs commonly used by adolescents, THC and nicotine .

Understanding mechanisms underlying sex differences in motivation for alcohol and response to stress

Our lab has found that female rodents consistently show elevated alcohol-motivated behaviors relative to males, and that these effects are magnified in the context of stress. Moreover, we have found that these sex differences are largely not dependent upon differences in gonadal hormones. Thus, we have been investigating differences in brain activation patterns between males and females after stressor-induced reinstatement of alcohol seeking and have found sex-specific brain activation patterns. The causal role of these neural activity differences in producing sex specific behaviors is being actively investigated.

Reinforcing and cognitive effects of cannabinoids in adolescence and adulthood

We have established IV self-administration of both a synthetic cannabinoid and THC in adolescent and adult rodents. We have determined that there are sex specific effects of adolescent THC self-administration on working memory in adulthood (after prolonged abstinence) and that we can observe cue-induced reinstatement and incubation of craving for cannabinoids. Ongoing studies are determining the neural mechanisms underlying long-lasting changes in cognitive function after cannabinoid exposure using molecular approaches and in vivo calcium imaging of prefrontal cortical neural activity. We are also investigating interactions between cannabinoid and nicotine self-administration, and how access to both drugs may promote cannabis use.

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