NIDA Center

Molecular Basis of Drug Addiction
Pharmacology 534 - Autumn 2006

C Chavkin, K Mackie, N Stella, J Neumaier, and P Phillips - Instructors

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.

3:30-5:30 PM
Introduction - Neural Substrates of Addiction (PP) Vanderschuren LJ, Everitt BJ (2005) Behavioral and neural mechanisms of compulsive drug seeking. Eur J Pharmacol 526, 77-88.
Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162, 1403-13.
Nestler EJ (2005) Is there a common molecular pathway for addiction? Nat Neurosci 8, 1445-9.
3:30-5:30 PM
Nicotine Addiction (CC) Wonnacott S, Sidhpura N, Balfour DJ. (2005) Nicotine: from molecular mechanisms to behaviour. Curr Opin Pharmacol. 5:53-9.
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.
Brunzell DH, Chang JR, Schneider B, Olausson P, Taylor JR, Picciotto MR. (2006) beta2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice. Psychopharmacology 184:328-38.
3:30-5:30 PM
Transporters, sensitization, and Drug Self-administration (JN) 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.
Ferguson SM, Fasano S, Yang P, Brambilla R, Robinson TE (2006) Knockout of ERK1 Enhances Cocaine-Evoked Immediate Early Gene Expression and Behavioral Plasticity. Neuropsychopharmacology. 2006 Jan 11; [Epub ahead of print]
Mateo Y, Lack CM, Morgan D, Roberts DC, Jones SR (2005) Reduced dopamine terminal function and insensitivity to cocaine following cocaine binge self-administration and deprivation. Neuropsychopharmacology 30:1455-1463.
3:30-5:30 PM
Retrograde Messengers (NS) Wilson RI, Nicoll RA. (2002) Endocannabinoid signaling in the brain. Science. 296:678-82.
Makara JK, Mor M, Fegley D, Szabo SI, Kathuria S, Astarita G, Duranti A, Tontini A, Tarzia G, Rivara S, Freund TF, Piomelli D. (2005) Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus. Nat Neurosci. 8:1139-41.
Hentges ST, Low MJ, Williams JT. (2005) Differential regulation of synaptic inputs by constitutively released endocannabinoids and exogenous cannabinoids. J Neurosci. 25:9746-51.
3:30-5:30 PM
Rimonabant and Cocaine (KM)
3:30-5:30 PM
Dopamine: D2 receptors in addiction (PP) 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.
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.
Nader MA, Morgan D, Gage HD, Nader SH, Calhoun TL, Buchheimer N, Ehrenkaufer R, Mach RH (2006) PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys. Nat Neurosci 9, 1050-6.
Graham DL, Hoppenot R, Hendryx A, Self DW (2006) Differential ability of D1 and D2 dopamine receptor agonists to induce and modulate expression and reinstatement of cocaine place preference in rats. Psychopharmacology [Epub ahead of print].
3:30-5:30 PM
Stress, affective disorders and drug abuse Reinstatement (JN) Bossert JM, Ghitza UE, Lu L, Epstein DH, Shaham Y (2005) Neurobiology of relapse to heroin and cocaine seeking: an update and clinical implications. Eur J Pharmacol 526:36-50.
Boutrel B, Kenny PJ, Specio SE, Martin-Fardon R, Markou A, Koob GF, de Lecea L (2005) Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior. Proc Natl Acad Sci U S A 102:19168-19173.
Sorge RE, Stewart J (2005) The contribution of drug history and time since termination of drug taking to footshock stress-induced cocaine seeking in rats. Psychopharmacology (Berl) 183:210-217.
Kippin TE, Fuchs RA, See RE (2006) Contributions of prolonged contingent and noncontingent cocaine exposure to enhanced reinstatement of cocaine seeking in rats. Psychopharmacology (Berl) 187:60-67.
3:30-5:30 PM
Proteomic and high throughput approaches to studying drugs of abuse (KM)
11/23/06 No Class -- Thanksgiving  
3:30-5:30 PM
Genetics (CC) 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.
3:30-5:30 PM
Signal transduction plasticity (trafficking) (NS) Gales C, Rebois RV, Hogue M, Trieu P, Breit A, Hebert TE, Bouvier M. (2005) Real-time monitoring of receptor and G-protein interactions in living cells. Nat Methods. 2:177-84.
Mukhopadhyay S, Howlett AC. (2005) Chemically distinct ligands promote differential CB1 cannabinoid receptor-Gi protein interactions. Mol Pharmacol. 67:2016-24.
3:30-5:30 PM
wrap up session (ALL) Deroche-Gamonet V, Belin D, Piazza PV. (2004) Evidence for addiction-like behavior in the rat. Science. 305(5686):1014-7.