Department of Psychiatry
Penn Behavioral Health

Center for Studies of Addiction

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Brain-Behavioral Vulnerabilities Laboratory

Research Areas

The research focus of the Brain-Behavioral Vulnerabilities (BBV) Laboratory is the vulnerability to relapse, and to addiction itself. In the view of BBV investigators, vulnerability is tied to the function (and dysfunction) of two critical, interactive, brain systems: 1) the ancient brain "GO!" system, providing the powerful motivation for natural rewards such as food and sex, and 2) the brain's inhibitory or "STOP!" systems, responsible for modulating the downstream limbic "GO!" regions.

With regard to the "GO!" vulnerabilities, the BBV has used functional imaging approaches (currently BOLD and perfusion fMRI) to show that conditioned drug cues (for cocaine, nicotine, heroin, and marijuana) can trigger limbic activation and drug desire ("craving"). This learned response to drug cues may lead to relapse in those who are addicted, and may also help propel vulnerable individuals toward addiction. The BBV has thus initiated ongoing projects attempting to modulate the brain-behavioral response to drug cues with medications (GABAergics for cocaine and nicotine cues; dronnabinol for marijuana cues, and oral methadone or depot naltrexone for opiate cues) and/or behavioral strategies for inhibition of cue-triggered craving.

With regard to "STOP!" vulnerabilities, BBV investigators have identified frontal deficits (hypoactivity and hypodense gray matter) in cocaine patients and have linked these deficits to addiction-relevant behaviors common in addicted adult populations (poor-decision making, increased risk-taking, poor inhibition, and poor affect regulation). Division researchers are currently characterizing structural (gray matter; white matter) and functional (perfusion) features in the "STOP!" circuitry of addicted adult populations, and will be using this information to help predict relapse and/or screen candidate medications targeting "STOP!" deficits.

The BBV has recently expanded its study of brain-behavioral vulnerability to adolescents-at-risk for addiction. This target group is critical for etiologic understanding, to determine which brain "differences" observed in addicted adults may actually pre-date and pre-dispose drug use -- offering rational targets for prevention of these chronic and painful disorders.

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