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Emerging Somatic Therapies for the Addicted Patient ,[object Object],[object Object],[object Object]
OVERVIEW ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Inhibitory/Control Reward Memory/Learning Functional Neuroanatomy of Addiction
Converging Acute Actions of Drugs of Abuse on the Ventral Tegmental Area and Nucleus Accumbens From: Nestler EJ,  Nat Neurosci , 2005, 8:1445-1449.
Ventral Pallidum NA Core PFCortex VTA Basolateral Amygdala MDthalamus Extended Amygdala Central amydala BNST NA Shell Dopamine GABA glutamate Circuitry Mediating Goal-directed Behavior ?? Amygdala - FEAR- motivated behaviors Nucleus Accumbens - Reward-motivated behaviors Prefrontal Cortex - Valence of stimulus Expression of motivated behavior Extended Amygdala - Stressor-induced behaviors Functional Neuroanatomy of Addiction
Pharmacotherapy:  New Targets --- NK1 ,[object Object],[object Object],[object Object],[object Object]
Pharmacotherapy: New Targets --- NK1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Positive and negative affective stimuli (IAPS) Negative Positive Pharmacotherapy: New Targets --- NK1 Courtesy of  Markus Heilig, M.D., Ph.D.  Clinical Director NIAAA/NIH
Attenuated fMRI responses to negative affective stimuli following treatment with LY686017  (George et al, Science 2008) Placebo LY686017 Courtesy of  Markus Heilig, M.D., Ph.D.  Clinical Director NIAAA/NIH Inferior frontal gyus/insula Parahippocampal gyrus Inferior frontal gyrus Middle temporal gyrus p < 0.001 p < 0.01
Up-regulated fMRI responses to positive affective stimuli  following treatment with LY686017  (George et al, Science 2008) Placebo LY686017 Courtesy of  Markus Heilig, M.D., Ph.D.  Clinical Director NIAAA/NIH Anterior cingulate/ caudate Thalamus Caudate (head) Lingual gyrus Nucleus accumbens/ putamen p < 0.001 p < 0.01
Pharmacotherapy: New Targets --- D3 ,[object Object],[object Object],[object Object]
Pharmacotherapy: New Targets --- Dopamine Beta Hydroxylase ,[object Object],[object Object],[object Object]
Pharmacotherapy: New Targets --- Adenosine A2A  ,[object Object],[object Object],[object Object],[object Object],[object Object]
Pharmacotherapy: New Targets --- mGluR-1  ,[object Object],[object Object],[object Object],[object Object],[object Object]
Pharmacotherapy : New Targets --- Glycine ,[object Object],[object Object],[object Object]
Pharmacotherapy: Semi-New Targets --- Cannabinoid 1 (CB1) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Pharmacotherapy: Old Targets Revisited --- Opioid  ,[object Object],[object Object]
Pharmacotherapy: Old Targets Revisited --- GABA ,[object Object],[object Object],[object Object]
Immunotherapy
Immunotherapy ,[object Object],[object Object],[object Object],[object Object]
Immunotherapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Nanotechnology ,[object Object],[object Object],[object Object]
Blood brain barrier (BBB) ,[object Object],[object Object],[object Object],[object Object],Function of BBB Compliments  of  Indrijat Roy, Ph.D. Receptor Mediated transport   –   Coupling of biomolecules (eg. insulin, insulin-like growth factor (IGF), leptin, transferrin) to surfaces which bind to cell receptors, are internalized and transported into brain. Strategies for overcoming BBB www.photonics.buffalo.edu The Institute for Lasers, Photonics and Biophotonics
Nanoplex ,[object Object],[object Object],[object Object],[object Object],[object Object],Compliments  of  Indrijat Roy, Ph.D. Gene Silencing e.g. DARPP-32 in Addictions www.photonics.buffalo.edu The Institute for Lasers, Photonics and Biophotonics
Gold nanorod (GNR) – fluorescent siRNA Nanoplex: Optical tracking of time dependent transport across BBB using in vitro model Compliments  of  Indrijat Roy, Ph.D. Confocal images of fluorescent siRNA showing enhanced staining of cells with time, thus indicating BBB transport www.photonics.buffalo.edu The Institute for Lasers, Photonics and Biophotonics
Nanoparticle mediated gene silencing: Implications in drug addiction therapy Compliments  of  Indrijat Roy, Ph.D. Gene silencing efficiency of gold nanorod  (GNR)-siRNA nanoplex is higher than that  obtained using commercial agent (siPORT) www.photonics.buffalo.edu The Institute for Lasers, Photonics and Biophotonics
Gene Therapy ,[object Object],[object Object],[object Object]
Gene Therapy Complements of  Scott J. Russo, M.D., Ph.D.
Gene Therapy ,[object Object],[object Object]
Genetically Directed Therapy ,[object Object],[object Object],[object Object],[object Object]
Stem Cells ,[object Object],[object Object],Stem Cell: Paul Leonard/Photo Researchers
Nuerostimulation ,[object Object],[object Object]
TMS
TMS
TMS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
TMS ,[object Object],[object Object],[object Object],[object Object]
DBS
DBS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
DBS Ncl.   accumbens Courtesy of  Jens Kuhn, M.D.
The machine does not isolate man from the great problems of nature but plunges him more deeply into them.  ~Saint-Exupéry,  Wind, Sand, and Stars , 1939

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Emerging Somatic Therapies for the Addicted Patient

  • 1.
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  • 3. Inhibitory/Control Reward Memory/Learning Functional Neuroanatomy of Addiction
  • 4. Converging Acute Actions of Drugs of Abuse on the Ventral Tegmental Area and Nucleus Accumbens From: Nestler EJ, Nat Neurosci , 2005, 8:1445-1449.
  • 5. Ventral Pallidum NA Core PFCortex VTA Basolateral Amygdala MDthalamus Extended Amygdala Central amydala BNST NA Shell Dopamine GABA glutamate Circuitry Mediating Goal-directed Behavior ?? Amygdala - FEAR- motivated behaviors Nucleus Accumbens - Reward-motivated behaviors Prefrontal Cortex - Valence of stimulus Expression of motivated behavior Extended Amygdala - Stressor-induced behaviors Functional Neuroanatomy of Addiction
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  • 8. Positive and negative affective stimuli (IAPS) Negative Positive Pharmacotherapy: New Targets --- NK1 Courtesy of Markus Heilig, M.D., Ph.D. Clinical Director NIAAA/NIH
  • 9. Attenuated fMRI responses to negative affective stimuli following treatment with LY686017 (George et al, Science 2008) Placebo LY686017 Courtesy of Markus Heilig, M.D., Ph.D. Clinical Director NIAAA/NIH Inferior frontal gyus/insula Parahippocampal gyrus Inferior frontal gyrus Middle temporal gyrus p < 0.001 p < 0.01
  • 10. Up-regulated fMRI responses to positive affective stimuli following treatment with LY686017 (George et al, Science 2008) Placebo LY686017 Courtesy of Markus Heilig, M.D., Ph.D. Clinical Director NIAAA/NIH Anterior cingulate/ caudate Thalamus Caudate (head) Lingual gyrus Nucleus accumbens/ putamen p < 0.001 p < 0.01
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  • 25. Gold nanorod (GNR) – fluorescent siRNA Nanoplex: Optical tracking of time dependent transport across BBB using in vitro model Compliments of Indrijat Roy, Ph.D. Confocal images of fluorescent siRNA showing enhanced staining of cells with time, thus indicating BBB transport www.photonics.buffalo.edu The Institute for Lasers, Photonics and Biophotonics
  • 26. Nanoparticle mediated gene silencing: Implications in drug addiction therapy Compliments of Indrijat Roy, Ph.D. Gene silencing efficiency of gold nanorod (GNR)-siRNA nanoplex is higher than that obtained using commercial agent (siPORT) www.photonics.buffalo.edu The Institute for Lasers, Photonics and Biophotonics
  • 27.
  • 28. Gene Therapy Complements of Scott J. Russo, M.D., Ph.D.
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  • 32.
  • 33. TMS
  • 34. TMS
  • 35.
  • 36.
  • 37. DBS
  • 38.
  • 39. DBS Ncl. accumbens Courtesy of Jens Kuhn, M.D.
  • 40. The machine does not isolate man from the great problems of nature but plunges him more deeply into them.  ~Saint-Exupéry, Wind, Sand, and Stars , 1939