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Molecular Basis of Drug Addiction
Pharmacology 534 - Autumn 2010

C Chavkin, 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.

9/30/10
3:30-5:30 PM
Introduction (Chavkin) Thomsen M, Hall FS, Uhl GR, Caine SB. (2009) Dramatically decreased cocaine self-administration in dopamine but not serotonin transporter knock-out mice. J Neurosci. 29(4):1087-92
 
Thomsen M, Han DD, Gu HH, Caine SB. (2009) Lack of cocaine self-administration in mice expressing a cocaine-insensitive dopamine transporter. J Pharmacol Exp Ther. 331(1):204-11.
 
Kasanetz F, Deroche-Gamonet V, Berson N, Balado E, Lafourcade M, Manzoni O, Piazza PV. (2010) Transition to addiction is associated with a persistent impairment in synaptic plasticity. Science. 328(5986):1709-12.
10/7/10
3:30-5:30 PM
Dopamine D2 receptors in addiction (Phillips) Volkow ND et al (2009) Imaging dopamine's role in drug abuse and addiction. Neuropharmacology 56:3-8 [review].
 
Morgan D et al (2002) Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration. Nat Neurosci 5:169-74.
 
Volkow ND et al (2006) High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. ArchGen Psychiatry 63:999-1008.
10/14/10
3:30-5:30 PM
Endocannabinoid signalling (Stella) Wang L, Liu J, Harvey-White J, Zimmer A, Kunos G. (2003) Endocannabinoid signaling via cannabinoid receptor 1 is involved in ethanol preference and its age-dependent decline in mice. Proc Natl Acad Sci U S A. 100(3):1393-8.
 
Katona I, Freund TF (2008) Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med. 14(9):923-30.
 
Orio L, Edwards S, George O, Parsons LH, Koob GF. (2009) A role for the endocannabinoid system in the increased motivation for cocaine in extended-access conditions. J Neurosci. 29(15):4846-57.
 
Ren Y, Whittard J, Higuera-Matas A, Morris CV, Hurd YL. (2009) Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. J Neurosci29(47):14764-9.
10/21/10
3:30-5:30 PM
Nicotine addiction risk(Chavkin) Changeux JP. (2010) Nicotine addiction and nicotinic receptors: lessons from genetically modified mice. Nat Rev Neurosci. 11(6):389-401. Review.
 
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.
 
Hartz SM, Bierut LJ. (2010) Genetics of addictions. Psychiatr Clin North Am. 33(1):107-24.
10/28/10
3:30-5:30 PM
Ecstasy (MDMA) Abuse (Neumaier) Biezonski, D. K. and Meyer, J. S. Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity. J Neurochem, 112, 951-962.
 
Doly, S., Bertran-Gonzalez, J., Callebert, J. et al. (2009) Role of serotonin via 5-HT2B receptors in the reinforcing effects of MDMA in mice. PLoS One, 4, e7952.
 
McGregor, I. S., Callaghan, P. D. and Hunt, G. E. (2008) From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use? Br J Pharmacol, 154, 358-368.
11/4/10
3:30-5:30 PM
Hallucinogens (Neumaier) Gonzalez-Maeso, J. and Sealfon, S. C. (2009) Psychedelics and schizophrenia. Trends Neurosci, 32, 225-232.
 
Gonzalez-Maeso, J., Ang, R. L., Yuen, T. et al. (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature, 452, 93-97.
 
Gonzalez-Maeso, J., Weisstaub, N. V., Zhou, M. et al. (2007) Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron, 53, 439-452.
11/10/10
3:30-5:30 PM
Cellular mechanisms of stress induced relapse (Lemos) 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.
 
Saal D, Dong Y, Bonci A, Malenka RC. (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron. 37(4):577-82.
 
Shalev U, Erb S, Shaham Y. (2010) Role of CRF and other neuropeptides in stress-induced reinstatement of drug seeking. Brain Res. 1314:15-28.
11/18/10
3:30-5:30 PM
Cannabinoid Receptor Signal Transduction (Horne) Clapper JR, Mangieri RA, Piomelli D. (2009) The endocannabinoid system as a target for the treatment of cannabis dependence. Neuropharmacology. 56 Suppl 1:235-43
 
Schlosburg JE, Blankman JL, Long JZ, Nomura DK, Pan B, Kinsey SG, Nguyen PT, Ramesh D, Booker L, Burston JJ, Thomas EA, Selley DE, Sim-Selley LJ, Liu QS, Lichtman AH, Cravatt BF. (2010) Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nat Neurosci. 13(9):1113-9.
 
Monory K, Blaudzun H, Massa F, Kaiser N, Lemberger T, Schütz G, Wotjak CT, Lutz B, Marsicano G. (2007) Genetic dissection of behavioural and autonomic effects of Delta(9)-tetrahydrocannabinol in mice. PLoS Biol. 5(10):e269.
11/23/10 The neural circuitry of drug seeking (Willuhn) Belin D, Everitt BJ. (2008) Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum. Neuron. 57(3):432-41.
 
Di Ciano P, Everitt BJ. (2004) Direct interactions between the basolateral amygdala and nucleus accumbens core underlie cocaine-seeking behavior by rats. J Neurosci. 24(32):7167-73.
 
Everitt BJ, Robbins TW. (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci. 8(11):1481-9. Review.
12/2/10
3:30-5:30 PM
Glutamate homeostasis in addiction(Phillips) Kalivas PW (2009) The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci 10:561-72 [review].
 
Baker DA et al (2003) Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat Neurosci 6:743-9.
 
Moussawi K et al (2009) N-Acetylcysteine reverses cocaine-induced metaplasticity. Nat Neurosci 12:182-9.
 
LaRowe SD et al (2007) Is cocaine desire reduced by N-acetylcysteine? Am J Psychiatry 164:1115-7. 
12/9/10
3:30-5:30 PM
Glutamate plasticity and the incubation of drug craving (Zweifel) Grimm JW, Hope BT, Wise RA, Shaham Y. (2001) Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature. Jul 12;412(6843):141-2
 
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. Jul 3;454(7200):118-21.
 
Mameli M, Halbout B, Creton C, Engblom D, Parkitna JR, Spanagel R, Lüscher C. (2009) Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc. Nat Neurosci. Aug;12(8):1036-41.
12/16/10
3:30-5:30 PM
Final Session (wrap up discussion of key concepts and future directions)