Front Behav Neurosci. 2013; 7: 206.
Pathological gambling [PG—now termed “gambling disorder” in DSM-5 (APA, 2013; Petry et al., 2013)] is characterized by maladaptive patterns of gambling that are associated with significant impairments in functioning. Over the past decade, significant advances have been made in understanding the pathophysiology of PG (Potenza, 2013). Similarities between PG and substance-use disorders (Petry, 2006; Potenza, 2006; Leeman and Potenza, 2012) prompted the reclassification of PG in DSM-5 as an addictive disorder (rather than an impulse-control disorder, as was the case in DSM-IV).
Multiple neurotransmitter systems have been implicated in PG including serotonergic, noradrenergic, dopaminergic, opioidergic, and glutamatergic (Potenza, 2013). An understanding of these systems as they relate to PG is important clinically for drug development as presently there are no FDA-approved medications with indications for PG. Dopamine has long been implicated in substance addictions and early articles postulated a similarly important role for dopamine in PG (Potenza, 2001). However, a precise role for dopamine in PG remains unclear. Studies of cerebrospinal fluid samples indicated low levels of dopamine and high levels of dopamine metabolites in PG, raising the possibility of increased dopamine turnover (Bergh et al., 1997). However, medications that target dopamine function have not demonstrated clinical effects in PG. For example, medications that block dopamine D2-like receptor function (e.g., olanzapine) have shown negative results in small, randomized clinical trials (Fong et al., 2008; McElroy et al., 2008). Furthermore, a D2-like dopamine receptor antagonist widely used in the treatment of psychotic disorders (haloperidol) was found to increase gambling-related motivations and behaviors in individuals with PG (Zack and Poulos, 2007). However, administration of the pro-dopaminergic (and pro-adrenergic) drug amphetamine also led to increased gambling-related thoughts and behaviors in PG (Zack and Poulos, 2004).
Recent imaging studies have begun to use radioligands and positron-emission tomography to investigate dopamine function in PG. In contrast to findings in cocaine dependence in which between-group differences were observed in [11C]raclopride-binding in the striatum, similar levels were observed in PG and comparison subjects by two investigative groups (Linnet et al., 2010, 2011; Clark et al., 2012). Similarly, no between-group difference between PG and comparison subjects was observed using [11C]raclopride or the D3-preferring agonist-radioligand [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) (Boileau et al., 2013). However, in these studies, relationships with mood-related or generalized impulsivity, disadvantageous decision-making or problem-gambling severity were reported, suggesting that dopamine function may relate to specific aspects of PG (Potenza and Brody, 2013). These findings are consistent with the idea that PG represents a heterogeneous condition and that identifying biologically relevant individual differences or subgroups may help advance treatment development or the appropriate targeting of therapeutic interventions.
A now well-documented association between dopamine and PG exists in Parkinson’s disease (PD) (Leeman and Potenza, 2011). Specifically, dopamine agonists (e.g., pramipexole, ropinirole) have been associated with PG and excessive or problematic behaviors in other domains (relating to sex, eating, and shopping) in individuals with PD (Weintraub et al., 2010). Furthermore, levodopa dosing has also been associated with these conditions in PD (Weintraub et al., 2010). However, factors seemingly unrelated to dopamine (e.g., age of PD onset, marital status and geographic location) have also been associated with these conditions in PD (Voon et al., 2006; Weintraub et al., 2006, 2010; Potenza et al., 2007), highlighting the complicated etiologies of these disorders. Nonetheless, in a study using [11C]raclopride, individuals with PD and PG as compared to those with PD alone demonstrated in the ventral (but not dorsal) striatum diminished D2-like binding at baseline and greater [11C]raclopride displacement during a gambling/decision-making task (suggesting greater dopamine release in the PG group during task performance) (Steeves et al., 2009). These findings are reminiscent of those suggesting blunted levodopa-induced displacement of [11C]raclopride in the ventral but not dorsal striatum in PD subjects who self-administer dopamine-replacement therapies to excess (as compared to those who do not) (Evans et al., 2006). As other findings have identified in association with behavioral addictions in PD (vs. those with PD alone) relatively reduced signal in the ventral striatum at baseline and during risk-taking (Rao et al., 2010), a question arises as to whether dopamine might relate to these processes in PD. Similar questions exist about the relatively blunted ventral striatal activation seen in non-PD PG in non-ligand-based imaging during simulated gambling (Reuter et al., 2005) and monetary reward processing (Balodis et al., 2012a; Choi et al., 2012). Although multiple studies have found blunted ventral striatal activation during the monetary-reward-anticipation phase (particularly during the performance of Monetary Incentive Delay tasks) across multiple addictive disorders [e.g., alcohol-use (Wrase et al., 2007; Beck et al., 2009) and tobacco-use (Peters et al., 2011) disorders] and other conditions characterized by impaired impulse control [e.g., binge-eating disorder (Balodis et al., 2013, in press)], other studies have found relatively increased ventral striatal activation during reward processing in individuals with PG and those with other addictions (Hommer et al., 2011; van Holst et al., 2012a), further raising questions about how striatal function contributes precisely to PG and addictions and how dopamine may be involved in these processes (Balodis et al., 2012b; Leyton and Vezina, 2012; van Holst et al., 2012b).
Although much of the radioligand-related data described above investigate D2/D3 receptor function, other dopamine receptors warrant consideration in PG. For example, on a rodent slot-machine task, the D2-like receptor agonist quinpirole enhanced erroneous expectations of reward on near-miss trials, and this effect was attenuated by a selective D4 (but not D3 or D2) dopamine receptor antagonist (Cocker et al., 2013). These preclinical findings complement human studies that suggest a role for the D4 dopamine receptor in gambling behaviors. For example, allelic variation at the gene coding for the D4 dopamine receptor has been associated with differential responses to levodopa-related increases in gambling behaviors (Eisenegger et al., 2010). These findings complement a larger literature linking the D4 dopamine receptor to impulsivity-related constructs and disorders like attention-deficit/hyperactivity disorder, albeit somewhat inconsistently (Ebstein et al., 1996; Gelernter et al., 1997; DiMaio et al., 2003). As preclinical (Fairbanks et al., 2012) and human (Sheese et al., 2012) data suggest gene-by-environment interactions involving the gene encoding the D4 dopamine receptor and aspects of impulsive or poorly controlled behaviors, further research should examine a role for the D4 dopamine receptor in PG, particularly in studies employing careful assessments of environmental and genetic factors. Although several D4-preferring/selective agonist compounds (e.g., PD-168,077 and CP-226,269) have been used in preclinical studies to study D4 receptors, additional research is needed to study human D4 dopamine receptors as might be accomplished through positron-emission-tomography studies—this represents an important line of future research (Bernaerts and Tirelli, 2003; Tarazi et al., 2004; Basso et al., 2005). Additionally, as the D1 dopamine receptor has been implicated in addictions like cocaine dependence (Martinez et al., 2009), a role for the D1 dopaminergic system in PG warrants exploration.
The above findings indicate that how dopaminergic function may contribute to PG and other addictions is currently at an early stage of understanding. Current data suggest that individual variability in dopamine function may obscure differences between PG and non-PG populations, with arguably the strongest between-group differences to date observed in a group with dopaminergic pathology (PD). The individual characteristics (e.g., impulsivity, decision-making and gambling-related behaviors) linked to dopamine function in PG and non-PG subjects also warrant consideration from a clinical perspective and suggest that these might represent novel treatment targets that link particularly closely to biological function [raising the possibility that they may be particularly amenable to targeting with medications (Berlin et al., 2013)]. Additionally, other potential endophenotypes like compulsivity (Fineberg et al., 2010, in press) warrant consideration given their preliminary links to treatment outcome in PG (Grant et al., 2010). Additionally, systems that may regulate dopamine function warrant further consideration in treatment development. For example, in randomized clinical trials, opioid antagonists like nalmefene and naltrexone have been found to be superior to placebo in treating PG (Grant et al., 2006, 2008b), particularly amongst individuals with strong gambling urges or familial histories of alcoholism (Grant et al., 2008a). Similarly, glutamatergic systems warrant consideration in this regard (Kalivas and Volkow, 2005), with preliminary data linking the neutraceutical n-acetyl cysteine to positive treatment outcome in PG (Grant et al., 2007). As dissecting the dopamine system is providing insight into PG, similar approaches should be used to investigate serotonin function in PG (Potenza et al., 2013), particularly given inconsistent findings with serotonergic medications in the treatment of PG (Bullock and Potenza, 2012). A systematic approach to investigating the neurobiology and clinical characteristics of PG should help advance prevention and treatment strategies for PG.
Dr. Marc N. Potenza has no financial conflicts of interest with respect to the content of this manuscript and has received financial support or compensation for the following: Dr. Marc N. Potenza has consulted for and advised Boehringer Ingelheim, Ironwood, and Lundbeck; has consulted for and has financial interests in Somaxon; has received research support from Mohegan Sun Casino, the National Center for Responsible Gaming, Forest Laboratories, Ortho-McNeil, Oy-Control/Biotie, Psyadon, Glaxo-SmithKline, the National Institutes of Health and Veteran’s Administration; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; has consulted for law offices and the federal public defender’s office in issues related to impulse control disorders; provides clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; has performed grant reviews for the National Institutes of Health and other agencies; has guest-edited journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts.
This study was funded by the National Institute on the Drug Abuse (NIDA) grant P20 DA027844, National Institute on Alcohol Abuse and Alcoholism grant RL1 AA017539, Connecticut Department of Mental Health and Addiction Services, Connecticut Mental Health Center, and the National Center for Responsible Gaming’s Center of Excellence in Gambling Research at Yale University.
- American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders. 5th Edn Washington, DC: American Psychiatric Association. [PubMed]
- Balodis I. M., Kober H., Worhunsky P. D., Stevens M. C., Pearlson G. D., Potenza M. N. (2012a). Diminished fronto-striatal activity during processing of monetary rewards and losses in pathological gambling. Biol. Psychiatry 71, 749–757.10.1016/j.biopsych.2012.01.006 [PMC free article] [PubMed] [Cross Ref]
- Balodis I. M., Kober H., Worhunsky P. D., Stevens M. C., Pearlson G. D., Potenza M. N. (2012b). Attending to striatal ups and downs in addictions. Biol. Psychiatry 72, e25–e26.10.1016/j.biopsych.2012.06.016 [PMC free article] [PubMed] [Cross Ref]
- Balodis I. M., Kober H., Worhunsky P. D., White M. A., Stevens M. C., Pearlson G. D., et al. (2013). Monetary reward processing in obese individuals with and without binge eating disorder. Biol. Psychiatry 73, 877–886.10.1016/j.biopsych.2013.01.014 [PMC free article] [PubMed] [Cross Ref]
- Balodis I. M., Grilo C. M., Kober H., Worhunsky P. D., White M. A., Stevens M. C., et al. (in press). A pilot study linking reduced fronto-striatal recruitment during reward processing to persistent bingeing following treatment for binge-eating disorder. Int. J. Eat. Disord.
- Basso A. M., Gallagher K. B., Bratcher N. A., Brioni J. D., Moreland R. B., Hsieh G. C., et al. (2005). Antidepressant-like effect of D(2/3) receptor-, but not D(4) receptor-activation in the rat forced swim test. Neuropsychopharmacology 30, 1257–1268.10.1038/sj.npp.1300677 [PubMed] [Cross Ref]
- Beck A., Schlagenhauf F., Wüstenberg T., Hein J., Kienast T., Kahnt T., et al. (2009). Ventral striatal activation during reward anticipation correlates with impulsivity in alcoholics. Biol. Psychiatry. 66, 734–742.10.1016/j.biopsych.2009.04.035 [PubMed] [Cross Ref]
- Bergh C., Eklund T., Sodersten P., Nordin C. (1997). Altered dopamine function in pathological gambling. Psychol. Med. 27, 473–475.10.1017/S0033291796003789 [PubMed] [Cross Ref]
- Berlin H. A., Braun A., Simeon D., Koran L. M., Potenza M. N., McElroy S. L., et al. (2013). A double-blind, placebo-controlled trial of topiramate for pathological gambling. World J. Biol. Psychiatry 14, 121–128.10.3109/15622975.2011.560964 [PubMed] [Cross Ref]
- Bernaerts P., Tirelli E. (2003). Facilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory consolidation of an inhibitory avoidance learned response in C57BL/6J mice. Behav. Brain Res. 142, 41–52.10.1016/S0166-4328(02)00371-6 [PubMed] [Cross Ref]
- Boileau I., Payer D., Chugani B., Lobo D., Behzadi A., Rusjan P. M., et al. (2013). The D2/3 dopamine receptor in pathological gambling: a positron emission tomography study with [11C]-(+)-propyl-hexahydro-naphtho-oxazin and [11C]raclopride. Addiction 108, 953–963.10.1111/add.12066 [PubMed] [Cross Ref]
- Bullock S. A., Potenza M. N. (2012). Pathological gambling: neuropsychopharmacology and treatment. Curr. Psychopharmacol. 1, 67–85 Available online at: http://www.benthamscience.com/contents.php?in=7497&m=February&y=2012. [PMC free article] [PubMed]
- Choi J.-S., Shin Y.-C., Jung W. H., Jang J. H., Kang D.-H., Choi C.-H., et al. (2012). Altered brain activity during reward anticipation in pathological gambling and obsessive-compulsive disorder. PLoS ONE 7:e45938.10.1371/journal.pone.0045938 [PMC free article] [PubMed] [Cross Ref]
- Clark L., Stokes P. R., Wu K., Michalczuk R., Benecke A., Watson B. J., et al. (2012). Striatal dopamine D2/D3 receptor binding in pathological gambling is correlated with mood-related impulsivity. Neuroimage 63, 40–46.10.1016/j.neuroimage.2012.06.067 [PMC free article] [PubMed] [Cross Ref]
- Cocker P. J., Le Foll B., Rogers R. D., Winstanley C. A. (2013). A selective role for Dopamine D4 receptors in modulating reward expectancy in a rodent slot machine task. Biol. Psychiatry. [Epub ahead of print].10.1016/j.biopsych.2013.08.026 [PubMed] [Cross Ref]
- DiMaio S., Grizenko N., Joober R. (2003). Dopamine genes and attention-deficit hyperactivity disorder: a review. J. Psychiatry Neurosci. 28, 27–38 Available online at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC161723/ [PMC free article] [PubMed]
- Ebstein R. P., Novick O., Umansky R., Priel B., Osher Y., Blaine D., et al. (1996). Dopamine D4 receptor (DRD4) exon III polymorphism associated with the human personality trait of novelty seeking. Nat. Gen. 12, 78–80.10.1038/ng0196-78 [PubMed] [Cross Ref]
- Eisenegger C., Knoch D., Ebstein R. P., Gianotti L. R., Sándor P. S., Fehr E. (2010). Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior. Biol. Psychiatry 67, 702–706.10.1016/j.biopsych.2009.09.021 [PubMed] [Cross Ref]
- Evans A. H., Pavese N., Lawrence A. D., Tai Y. F., Appel S., Doder M., et al. (2006). Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Ann. Neurol. 59, 852–858.10.1002/ana.20822 [PubMed] [Cross Ref]
- Fairbanks L. A., Way B. M., Breidenthal S. E., Bailey J. N., Jorgensen M. J. (2012). Maternal and offspring dopamine D4 receptor genotypes interact to influence juvenile impulsivity in vervet monkeys. Psychol. Sci. 23, 1099–1104.10.1177/0956797612444905 [PubMed] [Cross Ref]
- Fineberg N. A., Chamberlain S. R., Goudriaan A. E., Stein D. J., Vandershuren L., Gillan C. M., et al. (in press). New developments in human neurocognition: impulsivity and compulsivity. CNS Spectrums.
- Fineberg N. A., Potenza M. N., Chamberlain S. R., Berlin H., Menzies L., Bechara A., et al. (2010). Probing compulsive and impulsive behaviors, from animal models to endophenotypes; a narrative review. Neuropsychopharmacology 35, 591–604.10.1038/npp.2009.185 [PMC free article] [PubMed] [Cross Ref]
- Fong T., Kalechstein A., Bernhard B., Rosenthal R., Rugle L. (2008). A double-blind, placebo-controlled trial of olanzapine for the treatment of video poker pathological gamblers. Pharmacol. Biochem. Behav. 89, 298–303.10.1016/j.pbb.2007.12.025 [PubMed] [Cross Ref]
- Gelernter J., Kranzler H., Coccaro E., Siever L., New A., Mulgrew C. L. (1997). D4 dopamine-receptor (DRD4) alleles and novelty-seeking in substance-dependent, personality-disorder and control subjects. Am. J. Hum. Genet. 61, 1144–1152.10.1086/301595 [PMC free article] [PubMed] [Cross Ref]
- Grant J. E., Chamberlain S. R., Odlaug B. L., Potenza M. N., Kim S. W. (2010). Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study. Psychopharmacology (Berl) 212, 603–612.10.1007/s00213-010-1994-5 [PMC free article] [PubMed] [Cross Ref]
- Grant J. E., Kim S. W., Hollander E., Potenza M. N. (2008a). Predicting response to opiate antagonists and placebo in the treatment of pathological gambling. Psychopharmacology 200, 521–527.10.1007/s00213-008-1235-3 [PMC free article] [PubMed] [Cross Ref]
- Grant J. E., Kim S. W., Hartman B. K. (2008b). A double-blind, placebo-controlled study of the opiate antagonist naltrexone in the treatment of pathological gambling urges. J. Clin. Psychiatry 69, 783–789.10.4088/JCP.v69n0511 [PubMed] [Cross Ref]
- Grant J. E., Kim S. W., Odlaug B. L. (2007). N-Acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol. Psychiatry 62, 652–657.10.1016/j.biopsych.2006.11.021 [PubMed] [Cross Ref]
- Grant J. E., Potenza M. N., Hollander E., Cunningham-Williams R. M., Numinen T., Smits G., et al. (2006). Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am. J. Psychiatry 163, 303–312.10.1176/appi.ajp.163.2.303 [PubMed] [Cross Ref]
- Hommer D. W., Bjork J. M., Gilman J. M. (2011). Imaging brain response to reward in addictive disorders. Ann. N.Y. Acad. Sci. 1216, 50–61.10.1111/j.1749-6632.2010.05898.x [PubMed] [Cross Ref]
- Kalivas P. W., Volkow N. D. (2005). The neural basis of addiction: a pathology of motivation and choice. Am. J. Psychiatry 162, 1403–1413.10.1176/appi.ajp.162.8.1403 [PubMed] [Cross Ref]
- Leeman R. F., Potenza M. N. (2011). Impulse control disorders in Parkinson’s disease: clinical characteristics and implications. Neuropsychiatry 1, 133–147.10.2217/npy.11.11 [PMC free article] [PubMed] [Cross Ref]
- Leeman R. F., Potenza M. N. (2012). Similarities and differences between pathological gambling and substance use disorders: a focus on impulsivity and compulsivity. Psychopharmacology 219, 469–490.10.1007/s00213-011-2550-7 [PMC free article] [PubMed] [Cross Ref]
- Leyton M., Vezina P. (2012). On cue: striatal ups and downs in addictions. Biol. Psychiatry 72, e21–e22.10.1016/j.biopsych.2012.04.036 [PubMed] [Cross Ref]
- Linnet J., Moller A., Peterson E., Gjedde A., Doudet D. (2011). Inverse association between dopaminergic neurotransmission and Iowa Gambling Task performance in pathological gamblers and healthy controls. Scand. J. Psychol. 52, 28–34.10.1111/j.1467-9450.2010.00837.x [PubMed] [Cross Ref]
- Linnet J., Peterson E., Doudet D. J., Gjedde A., Moller A. (2010). Dopamine release in ventral striatum of pathological gamblers losing money. Acta Psychiatr. Scand. 122, 326–333.10.1111/j.1600-0447.2010.01591.x [PubMed] [Cross Ref]
- Martinez D., Slifstein M., Narendran R., Foltin R. W., Broft A., Hwang D. R., et al. (2009). Dopamine D1 receptors in cocaine dependence measured with PET and the choice to self-administer cocaine. Neuropsychopharmacology 34, 1774–1782.10.1038/npp.2008.235 [PMC free article] [PubMed] [Cross Ref]
- McElroy S., Nelson E. B., Welge J. A., Kaehler L., Keck P. E. (2008). Olanzapine in the treatment of pathological gambling: a negative randomized placebo-controlled trial. J. Clin. Psychiatry 69, 443–440.10.4088/JCP.v69n0314 [PubMed] [Cross Ref]
- Peters J., Bromberg U., Schneider S., Brassen S., Menz M., Banaschewski T., et al. (2011). Lower ventral striatal activation during reward anticipation in adolescent smokers. Am. J. Psychiatry 168, 540–549.10.1176/appi.ajp.2010.10071024 [PubMed] [Cross Ref]
- Petry N. M. (2006). Should the scope of addictive behaviors be broadened to include pathological gambling? Addiction 101, 152–160.10.1111/j.1360-0443.2006.01593.x [PubMed] [Cross Ref]
- Petry N. M., Blanco C., Auriacombe M., Borges G., Bucholz K., Crowley T. J., et al. (2013). An overview of and rationale for changes proposed for pathological gambling in Dsm-5. J. Gambling Stud. [Epub ahead of print].10.1007/s10899-013-9370-0 [PMC free article] [PubMed] [Cross Ref]
- Potenza M. N. (2001). The neurobiology of pathological gambling. Semin. Clin. Neuropsychiatry 6, 217–226.10.1053/scnp.2001.22929 [PubMed] [Cross Ref]
- Potenza M. N. (2006). Should addictive disorders include non-substance-related conditions? Addiction 101, 142–151.10.1111/j.1360-0443.2006.01591.x [PubMed] [Cross Ref]
- Potenza M. N. (2013). Neurobiology of gambling behaviors. Curr. Opin. Neurobiol. 23, 660–667.10.1016/j.conb.2013.03.004 [PMC free article] [PubMed] [Cross Ref]
- Potenza M. N., Brody A. L. (2013). Distinguishing D2/D3 dopaminergic contributions to addictions: commentary on boileau et al: the D2/3 dopamine receptor in pathological gambling: a PET study with [11C]-(+)-Propyl-Hexahydro-Naphtho-Oxazin and [11C]Raclopride. Addiction 108, 964–965.10.1111/add.12119 [PMC free article] [PubMed] [Cross Ref]
- Potenza M. N., Voon V., Weintraub D. (2007). Drug insights: impulse control disorders and dopamine therapies in Parkinson’s disease Nat. Clin. Practice Neuro. 3, 664–672.10.1038/ncpneuro0680 [PubMed] [Cross Ref]
- Potenza M. N., Walderhaug E., Henry S., Gallezot J. D., Planeta-Wilson B., Ropchan J., et al. (2013). Serotonin 1B receptor imaging in pathological gambling. World J. Biol. Psychiatry 14, 139–145.10.3109/15622975.2011.598559 [PMC free article] [PubMed] [Cross Ref]
- Rao H., Mamikonyan E., Detre J. A., Siderowf A. D., Stern M. B., Potenza M. N., et al. (2010). Decreased ventral striatal activity with impulse control disorders in Parkinson’s disease. Mov. Disord. 25, 1660–1669.10.1002/mds.23147 [PMC free article] [PubMed] [Cross Ref]
- Reuter J., Raedler T., Rose M., Hand I., Glascher J., Buchel C. (2005). Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nat. Neurosci. 8, 147–148.10.1038/nn1378 [PubMed] [Cross Ref]
- Sheese B. E., Rothbart M. K., Voelker P. M., Posner M. I. (2012). The Dopamine Receptor D4 Gene 7-repeat allele interacts with parenting quality to predict effortful control in 4-years-old children. Child Dev. Res. 2012:863242.10.1155/2012/863242 [PMC free article] [PubMed] [Cross Ref]
- Steeves T. D. L., Miyasaki J., Zurowski M., Lang A. E., Pellecchia G., van Eimeren T., et al. (2009). Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study. Brain 132, 1376–1385.10.1093/brain/awp054 [PMC free article] [PubMed] [Cross Ref]
- Tarazi F. I., Zhang K., Baldessarini R. J. (2004). Dopamine D4 receptors: beyond schizophrenia. J. Recept. Signal Transduct. Res. 24, 131–147.10.1081/RRS-200032076 [PubMed] [Cross Ref]
- van Holst R. J., Veltman D. J., Büchel C., van den Brink W., Goudriaan A. E. (2012a). Distorted expectancy coding in problem gambling: is the addictive in the anticipation? Biol. Psychiatry 71, 741–748.10.1016/j.biopsych.2011.12.030 [PubMed] [Cross Ref]
- van Holst R. J., Veltman D. J., van den Brink W., Goudriaan A. E. (2012b). Right on cue? Striatal reactivity in problem gamblers. Biol. Psychiatry 72, e23–e24.10.1016/j.biopsych.2012.06.017 [PubMed] [Cross Ref]
- Voon V., Hassan K., Zurowski M., Duff-Channing S., de Souza M., Fox S., et al. (2006). Prospective prevealence of pathological gabmling and medication association in Parkinson disease. Neurology 66, 1750–1752.10.1212/01.wnl.0000218206.20920.4d [PubMed] [Cross Ref]
- Weintraub D., Koester J., Potenza M. N., Siderowf A. D., Stacy M. A., Voon V., et al. (2010). Impulse control disorders in Parkinson’s disease: a cross-sectional study of 3090 patients. Arch. Neurol. 67, 589–595.10.1001/archneurol.2010.65 [PubMed] [Cross Ref]
- Weintraub D., Siderow A. D., Potenza M. N., Goveas J., Morales K. H., Duda J. E., et al. (2006). Dopamine agonist use is associated with impulse control disorders in Parkinson’s Disease. Arch. Neurol. 63, 969–973.10.1001/archneur.63.7.969 [PMC free article] [PubMed] [Cross Ref]
- Wrase J., Schlagenhauf F., Kienast T., Wüstenberg T., Bermpohl F., Kahnt T., et al. (2007). Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics. Neuroimage 35, 787–794.10.1016/j.neuroimage.2006.11.043 [PubMed] [Cross Ref]
- Zack M., Poulos C. X. (2004). Amphetamine primes motivation to gamble and gambling-related semantic networks in problem gamblers. Neuropsyhcopharmacology 29, 195–207.10.1038/sj.npp.1300333 [PubMed] [Cross Ref]
- Zack M., Poulos C. X. (2007). A D2 antagonist enhances the rewarding and priming effects of a gambling episode in pathological gamblers. Neuropsychopharmacology 32, 1678–1686.10.1038/sj.npp.1301295 [PubMed] [Cross Ref]