NIDA Center

Molecular Basis of Drug Addiction
Pharmacology 534 - Autumn 2008

Instructors: Chavkin, Neumaier, Phillips, Stella, Bruchas, Ferguson

The class format starts with an introduction by the instructor followed by a discussion of the papers listed. Students are expected to have read the papers beforehand, and come to class prepared to discuss the methods, experimental design, and principal conclusion of the assigned papers. The course is designed to enhance the critical reading skills of the students and to familiarize the students with the strengths and limits of the key techniques in this research area.

3:30-5:20 PM
Chavkin (Introduction) Deroche-Gamonet V, Belin D, Piazza PV. (2004) Evidence for addiction-like behavior in the rat. Science. 305(5686):1014-7.
Maskos U, Molles BE, Pons S, Besson M, Guiard BP, Guilloux JP, Evrard A, Cazala P, Cormier A, Mameli-Engvall M, Dufour N, Cloez-Tayarani I, Bemelmans AP, Mallet J, Gardier AM, David V, Faure P, Granon S, Changeux JP. (2005) Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors. Nature. 436:103-7.
Chen R, Tilley MR, Wei H, Zhou F, Zhou FM, Ching S, Quan N, Stephens RL, Hill ER, Nottoli T, Han DD, Gu HH (2006) Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter. Proc Natl Acad Sci U S A 103:9333-9338.
3:30-5:20 PM
Phillips: Dopamine D2 receptors in addiction Morgan D, Grant KA, Gage HD, Mach RH, Kaplan JR, Prioleau O, Nader SH, Buchheimer N, Ehrenkaufer RL, Nader MA (2002) Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration. Nat Neurosci. 5:169-74.
Volkow ND, Wang GJ, Begleiter H, Porjesz B, Fowler JS, Telang F, Wong C, Ma Y, Logan J, Goldstein R, Alexoff D, Thanos PK (2006) High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Arch Gen Psychiatry. 63:999-1008.
3:30-5:20 PM
Stella: endocannabinoid synthesis, signal transduction Straiker A, Mackie K. (2006) Cannabinoids, electrophysiology, and retrograde messengers: challenges for the next 5 years. AAPS J. 8(2):E272-6.
Blankman JL, Simon GM, Cravatt BF. (2007) A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol. 14(12):1347-56.
Lafourcade M, Elezgarai I, Mato S, Bakiri Y, Grandes P, Manzoni OJ. (2007) Molecular components and functions of the endocannabinoid system in mouse prefrontal cortex. PLoS ONE. 2(1):e709.
Nomura DK, Blankman JL, Simon GM, Fujioka K, Issa RS, Ward AM, Cravatt BF, Casida JE. (2008) Activation of the endocannabinoid system by organophosphorus nerve agents. Nat Chem Biol. 4:373-8.
3:30-5:20 PM
Neumaier: Stress mechanisms underlying depression, anxiety disorders and addiction Nestler EJ, Carlezon WA Jr. (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry. 59(12):1151-9.
Graham DL, Edwards S, Bachtell RK, DiLeone RJ, Rios M, Self DW. (2007) Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse. Nat Neurosci. 10(8):1029-37.
Wang B, You ZB, Rice KC, Wise RA. (2007) Stress-induced relapse to cocaine seeking: roles for the CRF(2) receptor and CRF-binding protein in the ventral tegmental area of the rat. Psychopharmacology (Berl). 193(2):283-94.
3:30-5:20 PM
Neumaier: Serotonin Nic Dhonnchadha BA, Cunningham KA. (2008) Serotonergic mechanisms in addiction-related memories. Behav Brain Res [Epub ahead of print]
Conrad KL, Tseng KY, Uejima JL, Reimers JM, Heng LJ, Shaham Y, Marinelli M, Wolf ME. (2008) Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving. Nature. 454(7200):118-21.
González-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M, Ge Y, Zhou Q, Sealfon SC, Gingrich JA. (2007) Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron. 53(3):439-52.
3:30-5:20 PM
Chavkin: Genetic approaches to identify addiction risk Kreek MJ, Nielsen DA, Butelman ER, LaForge KS. (2005) Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nat Neurosci. 8:1450-7. Review.
King MC, Motulsky AG. (2002) Human genetics. Mapping human history. Science. 298:2342-3. short comment on 'race' in genetic studies.
Johnson C, Drgon T, Liu QR, Walther D, Edenberg H, Rice J, Foroud T, Uhl GR. (2006) Pooled association genome scanning for alcohol dependence using 104,268 SNPs: Validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism. Am J Med Genet B Neuropsychiatr Genet. 2006
Proudnikov D, LaForge KS, Hofflich H, Levenstien M, Gordon D, Barral S, Ott J, Kreek MJ. (2006) Association analysis of polymorphisms in serotonin 1B receptor (HTR1B) gene with heroin addiction: a comparison of molecular and statistically estimated haplotypes. Pharmacogenet Genomics. 16:25-36.
3:30-5:20 PM
Stella: Cannabinoid Receptor Signal Transduction Heimann AS, Gomes I, Dale CS, Pagano RL, Gupta A, de Souza LL, Luchessi AD, Castro LM, Giorgi R, Rioli V, Ferro ES, Devi LA. (2007) Hemopressin is an inverse agonist of CB1 cannabinoid receptors. Proc Natl Acad Sci U S A104(51):20588-93.
Niehaus JL, Liu Y, Wallis KT, Egertová M, Bhartur SG, Mukhopadhyay S, Shi S, He H, Selley DE, Howlett AC, Elphick MR, Lewis DL. (2007) CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a. Mol Pharmacol. 2007 Dec;72(6):1557-66.
Nickl K, Gardner EE, Geiger S, Heilmann J, Seifert R. (2008) Differential coupling of the human cannabinoid receptors hCB(1)R and hCB(2)R to the G-protein Galpha(i2)beta(1)gamma(2). Neurosci Lett. 2008 Dec 5;447(1):68-72.
3:30-5:20 PM
Ferguson: Recent advances in modeling addiction in animals and testing theories of addiction Mulholland PJ, Chandler LJ. (2007) The thorny side of addiction: adaptive plasticity and dendritic spines. ScientificWorldJournal 7:9-21.
Pulipparacharuvil S, Renthal W, Hale CF, Taniguchi M, Xiao G, Kumar A, Russo SJ, Sikder D, Dewey CM, Davis MM, Greengard P, Nairn AC, Nestler EJ, Cowan CW. (2008) Cocaine regulates MEF2 to control synaptic and behavioral plasticity. Neuron 59(4):621-33.
Ferrario CR, Gorny G, Crombag HS, Li Y, Kolb B, Robinson TE. (2005) Neural and behavioral plasticity associated with the transition from controlled to escalated cocaine use. Biol Psychiatry. 58(9):751-9.
3:30-5:20 PM
Bruchas: Kinase cascades in Addiction Lu L, Koya E, Zhai H, Hope BT, Shaham Y. (2006) Role of ERK in cocaine addiction. Trends Neurosci. 29(12):695-703.
Lu L, Hope BT, Dempsey J, Liu SY, Bossert JM, Shaham Y. (2005) Central amygdala ERK signaling pathway is critical to incubation of cocaine craving. Nat Neurosci. 8(2):212-9.
Russo SJ, Bolanos CA, Theobald DE, DeCarolis NA, Renthal W, Kumar A, Winstanley CA, Renthal NE, Wiley MD, Self DW, Russell DS, Neve RL, Eisch AJ, Nestler EJ. (2007) IRS2-Akt pathway in midbrain dopamine neurons regulates behavioral and cellular responses to opiates. Nat Neurosci. 10(1):93-9.
11/27/08 No Class -- Thanksgiving  
3:30-5:20 PM
Phillips: Glutamate (last session) Tonic glutamate regulation in addiction Baker DA, McFarland K, Lake RW, Shen H, Tang XC, Toda S, Kalivas PW (2003) Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat Neurosci. 6:743-9.
Madayag A, Lobner D, Kau KS, Mantsch JR, Abdulhameed O, Hearing M, Grier MD, Baker DA (2007) Repeated N-acetylcysteine administration alters plasticity-dependent effects of cocaine. J Neurosci. 27:13968-76.
LaRowe SD, Myrick H, Hedden S, Mardikian P, Saladin M, McRae A, Brady K, Kalivas PW, Malcolm R (2007) Is cocaine desire reduced by N-acetylcysteine? Am J Psychiatry. 164:1115-7.