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The Neurobiology of Nicotine Dependence and Co-Morbid Psychiatric Disorders. George F. Koob, Ph.D. Athina Markou, Ph.D. Department of Neuropharmacology The Scripps Research Institute La Jolla, California. Criteria for Substance Dependence (DSM-IV).
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George F. Koob, Ph.D.
Athina Markou, Ph.D.
Department of Neuropharmacology
The Scripps Research Institute
La Jolla, California
From: Koob GF and Le Moal M, Science, 1997, 278:52-58.
From: Huston-Lyons D and Kornetsky C, Pharmacol Bioch Behav, 1992, 41:755-759.
Human data adapted from: Henningfield JR, Miyasato K and Jasinski DR, Pharmacol Biochem Behav
From: Watkins SS, Epping-Jordan MP, Koob GF and Markou A, Pharmacol Biochem Behav, 1999, 62:743-751.
From: Watkins SS, Epping-Jordan MP, Koob GF and Markou A, Pharmacol Biochem Behav, 1999, 62:743-751
From: Corrigall WA, Franklin FBJ, Coen KM, and Clarke PBS, Psychopharmacology, 1992, 107:285-289.[
with Dopamine and Glutamate Transmission
Nicotine activates nAChRs located on glutamate terminals in the ventral tegmental area (VTA)
Nicotine-stimulated glutamate release acts at glutamate receptors located on VTA dopamine neurons
Activation of glutamate receptors stimulates dopamine release into terminal regions, such as the nucleus accumbens
From: Kelley AE, Nature Med, 2002, 8:477-479.
“The notion of dependence on a drug, object, role, activity or any other stimulus-source requires the crucial feature of negative affect experienced in its absence. The degree of dependence can be equated with the amount of this negative affect, which may range from mild discomfort to extreme distress, or it may be equated with the amount of difficulty or effort required to do without the drug, object, etc.”
From: Russell MAH, What is dependence? In Edwards G (ed), Drugs and Drug Dependence, Lexington Books, Lexington, MA, 1976, pp. 182-187.
behavioral syndrome in humans
Adapted from: Markou A and Koob GF, Physiol Behav, 1992, 51:111-119.
Adapted from: Epping-Jordan MP, Watkins SS, Koob GF and Markou A, Nature, 1998, 393:76-79.
From: Epping-Jordan MP, Watkins SS, Koob GF and Markou A, Nature, 1998, 393:76-79.
From: Hildebrand BE, Nomikos GG, Hertel P, Schilstrom B and Svensson TH, Brain Res, 1998, 779:214-225.
From: Panagis G, Hildebrand BE, Svensson TH and Nomikos GG, Synapse, 2000, 35:15-25.
From: Cheeta S, Tucci S and File SE, Pharmacol Biochem Behav, 2001, 70:491-496.
From: Harrison AA, Liem YTB and Markou A, Neuropsychopharmacology, 2001, 25:55-71.
From: Kenny PJ, Gasparini F and Markou A, unpublished results.
Glutamatergic and GABAergic regulation of dopamine transmission in the VTA
Adapted from: Schoepp DD, J Pharmacol Exp Ther, 2001, 299:12-20.
Acetylcholinepedunculopontine tegmental nucleus
Dopaminenucleus accumbens, amygdala
Opioid Peptidesnucleus accumbens, amygdala, ventral tegmental area
Glutamateventral tegmental area
Corticotropin-Releasing Factor (???)
Lanca et al., 2000
Hildebrand et al., 1999Pangis et al., 2000
Malin et al., 1993Ise et al., 2000Watkins et al., 2000
Harrison et al., 2001Cheeta et al., 2001
Kenny et al., 2001
From: Schulkin J, McEwen BS and Gold PW, Neurosci Biobehav Rev, 1994, 18:385-396.
Cryan, Bruijnzeel, Skjei & Markou, Psychopharmacology, 168:347-358, 2003
From: Koob GF and Le Moal M, Neuropsychopharmacology, 2001, 24:97-129.
Heimer L and Alheid G, Piecing together the puzzle of basal forebrain anatomy. In: Napier TC, Kalivas PW and Hanin I (Eds), The Basal Forebrain: Anatomy to Function (series title: Advances in Experimental
Medicine and Biology, Vol. 295), Plenum Press, New York, 1991, pp. 1-42.Potential Substrates in the Extended Amygdala for the Motivational Effects of Drug Dependence
Amanda Harrison Paul Kenny
Laura O’ Dell