Biobehavioral Studies of Addiction and Neuropsychiatric Disorders

Behavioral Genetics Laboratory, McLean Hospital

William A. Carlezon Jr., Ph.D., Elena H. Chartoff, Ph.D., Edward G. Meloni, Ph.D., Rebecca J. Ralph-Williams, Ph.D., Mark S. Todtenkopf, Ph.D.

This multidisciplinary, preclinical research program explores in animal models how genes affect complex motivated behaviors. We are particularly interested in how experiences such as drug exposure or stress affect gene expression within the mesolimbic system (ventral tegmental area, nucleus accumbens) and cortical structures (frontal cortex, amygdala), and in turn how these molecular adaptations lead to alterations in behavior. In some cases, we mimic the effects of drug exposure or stress on gene expression through the use of engineered viral vectors, which allow us to transfer genes directly into select areas of rat brain. In other cases, we manipulate gene expression using genetically engineered mice. We use a variety of behavioral assays in rats and mice (place conditioning, rewarding brain stimulation, fear-potentiated startle, prepulse inhibition, forced swimming), each of which models various aspects of addiction or neuropsychiatric conditions such as depression, schizophrenia, and anxiety-related disorders.

Key words: addiction, anxiety, cocaine, dependence, depression, fear, model, mouse, opiates, schizophrenia, stimulants, rat.

Grant Support: NIDA: RO1 DA12736, Biobehavioral Mechanisms of Drug Reward and Addiction (WAC); RO3 DA13634, Role of Nucleus Accumbens Ca2+ Flux in Cocaine Reward (WAC); R21 DA14789, A Simple Model of Cocaine Withdrawal in Rats (WAC); NIMH: R01 MH63266, Role of Nucleus Accumbens CREB in Depression (WAC).

Program Site: Behavioral Genetics Laboratory, Mailman Research Center, McLean Hospital.

Program Director: William A. Carlezon Jr., Ph.D., Behavioral Genetics Laboratory, McLean Hospital, 115 Mill St., Belmont, MA 02478. e-mail address: carlezon@mclean.harvard.edu

Contact Person: William A. Carlezon Jr., Ph.D., phone: 617/855-2021, fax: 617/855-2023

Training Opportunities: Both pre- and post-doctoral training positions are available.

Representative Publications:

Andersen SL, Arvanitogiannis A, Pliakas AM, LeBlanc C, Carlezon WA Jr (2001) Altered responsiveness to cocaine in rats exposed to methylphenidate during early development. Nature Neuroscience, in press.

Carlezon WA Jr, Haile CN, Coopersmith R, Hayashi Y, Malinow R, Neve RL, Nestler EJ (2000) Distinct sites of opiate reward and aversion within the midbrain identified by a herpes simplex virus vector expressing GluR1. Journal of Neuroscience 20: RC62, 1-5

Carlezon WA Jr, Nestler EJ, Neve RL (2000) Viral-mediated gene transfer as a tool for neuropsychiatric research. Critical Reviews in Neurobiology 14: 47-68

Carlezon WA Jr, Pliakas AM, Parow AM, Cohen BM, Renshaw PF (2001) Behavioral effects of the citicoline (CDP-choline) metabolite cytidine in rats. Biological Psychiatry, in press

Carlezon WA Jr, Thome J, Olson VG, Lane-Ladd SB, Brodkin ES, Hiroi N, Duman RS, Neve RL, Nestler EJ. (1998) Regulation of cocaine reward by CREB. Science 282: 2272-2275

Pliakas AM, Carlson R, Neve RL, Konradi C, Nestler EJ, Carlezon WA Jr (2001) Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element binding protein expression in nucleus accumbens. Journal of Neuroscience 21: 7397-7403