S. Barak Caine, Ph.D.

Associate Professor of Psychology in the Department of Psychiatry

McLean Hospital
Alcohol & Drug Abuse Research Center
115 Mill St
Belmont, MA 02478
Telephone: 617-855-2258
Fax: 617- 855-3865
Email: barak@mclean.harvard.edu
Lab Website: Behavioral Science Laboratory
Predocs: 0 Postdocs: 1 Completed PhD's: 1

Much of my work is aimed at evaluating the roles of distinct monoamine transporters and receptor subtypes in the psychomotor and abuse-related effects of cocaine and amphetamine.  A primary goal is to assess the potential of novel compounds as candidate medications for the treatment of psychosis (e.g., schizophrenia) or as pharmacological adjuncts for the treatment of cocaine abuse and dependence.  Behavioral pharmacology is used to evaluate pharmacological mechanisms underlying the psychomotor stimulant, sensorimotor disruptive, discriminative stimulus and reinforcing effects of cocaine and related drugs. Novel compounds are evaluated in rats that self-administer cocaine to evaluate candidate pharmacotherapies for drug addiction.  Mice that are genetically altered as a result of either targeted mutations (“reverse genetics”) or ENU-induced mutagenesis (“forward genetics”) are studied in order to assess the role of mouse genes in addiction- or psychosis-related behaviors.  A new project is focused on genetic manipulations in rats that may complement studies of transgenic and knockout mice.  Major collaborations include studies of mice with targeted mutations in dopamine systems in collaboration with Ming Xu at the University of Cincinnati, studies of mice with random mutations in collaboration with Marc Caron at Duke University and Joe Takahashi at Northwestern University, and studies with novel cannabinoid ligands in rats in collaboration with Alex Makriyannis at Northeastern University.  Brain targets currently under investigation in the laboratory include dopamine transporters and receptors (D1, D2, D3), serotonin transporters, glutamate receptors (mGluR5), glycine transporters (GlyT1), cannabinoid (CB1) receptors and muscarinic (M1, M5) receptors.

References:

• Thomsen M, Fink-Jensen A, Woldbye W, Wörtwein G, Sager T, Holm R, Pepe L, Caine SB.  Effects of acute and chronic aripiprazole treatment on choice between cocaine self-administration and food under a concurrent schedule of reinforcement in rats. Psychopharmacology 2008: in press; on line DOI 10.1007/s00213-008-1245-1
• Caine SB, Thomsen M, Gabriel KI, Berkowitz JS, Gold LH, Koob GF, Tonegawa S, Zhang J, Xu M.  Lack of self-administration of cocaine in dopamine D1 receptor knockout mice.  Journal of Neuroscience 2007:27;13140-13150.
• Thomsen M, Wörtwein G, Woldbye DPD, Fink-Jensen A, Wess J, Caine SB. Decreased prepulse inhibition and increased sensitivity to muscarinic, but not dopaminergic drugs in a line of M5 muscarinic acetylcholine receptor knockout mice. Psychopharmacology 2007:192;97-110.
• Barrett AC, Negus SS, Mello NK, Caine SB.  Effect of GABA agonists and GABA-A receptor modulators on cocaine- and food-maintained responding and cocaine discrimination in rats.  Journal of Pharmacology and Experimental Therapeutics, 2005:315;858-871.
• Ralph RJ, Caine SB. Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: comparison of Sprague Dawley rats to Swiss Webster, 129X1/SvJ, C57BL/6J and DBA/2J Mice.  Journal of Pharmacology and Experimental Therapeutics 2005:312;733-741.