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Addiction is a debilitating disease that results in alterations in neuronal processes. My research is focused on the cellular adaptations of noradrenergic circuits to drugs of abuse (opiates, cannabinoids and psychostimulants). Chronic opiate use produces persistent changes in noradrenergic brain neurons resulting (locus coeruleus) in adverse effects including physical dependence and withdrawal. Repeated cannabinoid exposure results in transient increases in indices of noradrenergic activity. Preclinical studies are aimed at 1) developing novel opiate detoxification approaches for counteracting norepinephrine overactivity following withdrawal from opiates. Our research has also identified important interactions of opioids and stress-related peptides including corticotropin-releasing factor, an integral mediator of the stress response, on noradrenergic activity. For example, opiates sensitize the brain norepinephrine system to stress that may contribute to the maintenance of opiate abuse. Repeated cannabinoid exposure leads to anxiety-like behaviors that may predispose individuals to affective disorders.
Our laboratory employs state-of-the-art neuroanatomical approaches (pre- and post-embedding immunoelectron microscopy, confocal fluorescence microscopy, intracranial injections of tract-tracers for the identification of synaptic circuits), biochemical techniques (Western blot analysis, co-immunoprecipitation assays, microdialysis coupled with high performance liquid chromatography), molecular neuroscience (qRT-PCR), and behavioral pharmacology (tests for anxiety, depression, stress).
By understanding neural adaptations to drugs of abuse, novel pharmacotherapies can be developed to treat compulsive drug use and sustain recovery.
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