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S. Barak Caine, Ph.D.

Assistant Professor of Psychology in the Dept. of Psychiatry

McLean Hospital
Alcohol & Drug Abuse Rsrch Ctr
115 Mill St
Belmont, MA 02478
Telephone: 617-855-2258
Fax: 617- 855-2519
Email: barak@mclean.harvard.edu
Predocs: 1 Postdocs: 1 Completed PhD's: 0

  

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:

  • Caine SB, Koob GF (1993) Modulation of cocaine self- administration in the rat through D-3 dopamine receptors. Science 60:1814-1816.
  • Caine SB (1998) Cocaine abuse: Hard knocks for the dopamine hypothesis? Nature Neurosci. 1:90-92.
  • Caine SB, Negus SS, Mello NK, Patel S, Bristow L, Kulagowski J, Vallone D, Saiardi A, Borrelli E (2002) Role of dopamine D2-like receptors in cocaine self-administration: studies with D2 receptor mutant mice and novel D2 receptor antagonists. J. Neurosci. 22:2977-2988.
  • Tsai G, Ralph RJ, Martina M, Bergeron R, Berger-Sweeney J, Dunham KS, Jiang Z, Caine SB, Coyle J (2004) Gene knockout of GlyT1 transporter: characterization of the behavioral phenotype. Proc. Natl. Acad. Sci. 101:8485-90.
  • Ralph RJ, Caine SB. (2005) 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. J. Pharmacol. Exp. Ther. 312:733-741.