Browsing by Subject "Sensitization"

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    Behavioral and neurobiological consequences of intermittent exposure to addictive drugs.
    (2010-02) Rothwell, Patrick Eldredge
    These studies were undertaken to better understand how repeated exposure to addictive drugs leads to adaptations in brain function and behavior related to the development of addiction. They are predicated on evidence that the mere presence of a drug in the body is not the sole determinant of adaptation - rather, the pattern of drug exposure is a key variable, with intermittent exposure making the brain reward system increasingly sensitive to drugs and leaving individuals susceptible to relapse. These experiments were designed to examine whether events occurring during the offset of drug action may contribute to the unique effects of intermittent drug exposure. The first series of experiments develops a set of behavioral measures that can be used to resolve and quantify a state of acute withdrawal caused by the offset of drug action. The second series of experiments utilizes these measures to investigate whether recurrent episodes of acute withdrawal contribute to the development of psychomotor sensitization - a specific consequence of intermittent drug exposure related to adaptations in the brain reward system. The final series of experiments describes a specific synaptic adaptation in a key component of the brain reward system (the nucleus accumbens) that is caused by intermittent drug exposure, related to the development of psychomotor sensitization, and reversed by experiences linked to relapse. The results of these studies suggests new and provocative interactions between neural circuits mediating reward and aversion, which may help identify and explain forms of neural plasticity that underlie the development of drug addiction.
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    Impact of cocaine sensitization on GLT1 protein levels in the medial Prefrontal Cortex and Nucleus Accumbens Core
    (2022-05) Aruldas, Rachel; Buczek, Laura; Sade, Spencer
    Cocaine is an addictive stimulant that targets parts of the corticostriatal reward circuit like the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). The mPFC communicates with the NAc via glutamatergic projections which regulate reward-seeking behavior. Cocaine self-administration downregulates glutamate transporter 1 (GLT1) gene expression and disrupts this communication. We aimed to determine if cocaine impacts GLT1 protein levels in the mPFC and NAc core. Rats were given cocaine or saline injections for six days and a challenge injection on the seventh day. They were divided into groups based on the initial and challenge injections they received: cocaine & cocaine (c-c), cocaine & saline (c-s), saline & cocaine (s-c), saline & saline (s-s). The locomotion of rats was tracked for forty-five minutes following daily injections. On the seventh day, tissue from the rat’s NAc core (NAcC) and mPFC was extracted. Western Blots were used to quantify GLT-1 levels in the collected tissue. We hypothesized that group c-c would have the lowest GLT1 levels and group s-s would have the highest GLT1 levels as those rats had no cocaine exposure. Our results showed that cocaine sensitization had no impact on GLT1 expression levels in the mPFC and NAcC. These results will inform further research into the impact of cocaine sensitization vs self-administration on proteins in specific regions of the brain.