Guanfacine improves selective cognitive processes which may underlie salient treatment-related regulatory behaviors. Alpha2 agonists may therefore represent important agents for cocaine dependence.

Compared with placebo, the guanfacine group demonstrated attenuated anxiety and negative affect as well as improved performance on selective executive tests. This included fewer directional errors on the stop signal task, fewer errors on the extra-dimensional shift component of the IDED task and better attentional switching during verbal fluency. Guanfacine did not improve strategic working memory or peripheral memory.

Twenty-five early abstinent cocaine-dependent individuals were administered a battery of neurocognitive tasks on entry into treatment (baseline) and again following 3 weeks of either placebo or guanfacine treatment (up to 3 mg). Tasks included: Stop Signal, Stroop, 3-Dimentional Intra-dimensional/Extra-dimensional (IDED) task, Spatial Working Memory (SWM), Paired Associates Learning (PAL), Verbal Fluency and the Rey Auditory Verbal Learning Test (RAVLT).

Attenuation of adrenergic drive and cognitive enhancement, via stimulation of alpha2 pre- and post-synaptic receptors, may selectively enhance executive performance in early abstinent cocaine-dependent individuals. As these cognitive processes underpin important treatment-related behaviors, the alpha2 agonist, guanfacine HCl, may represent an effective pharmaco-therapeutic intervention.

References

Ahmadi, J, Kampman, K, Dackis, C ( 2006 ) Outcome predictors in cocaine dependence treatment trials . Am J Addict 15: 434 – 439 .

Google Scholar Crossref | Medline

Alexander, JK, Hillier, A, Smith, RM. ( 2007 ) Beta-adrenergic modulation of cognitive flexibility during stress . J Cogn Neurosci 19: 468 – 478 .

Google Scholar Crossref | Medline | ISI

Ambrose-Lanci, LM, Sterling, RC, Van Bockstaele, EJ ( 2010 ) Cocaine withdrawal-induced anxiety in females: Impact of circulating estrogen and potential use of delta-opioid receptor agonists for treatment . J Neurosci Res 88: 816 – 824 .

Google Scholar Medline

Arnsten, AF ( 1998 ) Catecholamine modulation of prefrontal cortical cognitive function . Trends Cogn Sci 2: 436 – 447 .

Google Scholar Crossref | Medline | ISI

Arnsten, AF ( 2011 ) Catecholamine influences on dorsolateral prefrontal cortical networks . Biol Psychiatry 69: e89 – e99 .

Google Scholar Crossref | Medline

Arnsten, AF, Contant, TA ( 1992 ) Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task . Psychopharmacology (Berl) 108: 159 – 169 .

Google Scholar Crossref | Medline

Arnsten, AF, Goldman-Rakic, PS ( 1985 ) Alpha 2-adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged nonhuman primates . Science 230: 1273 – 1276 .

Google Scholar Crossref | Medline | ISI

Arnsten, AF, Goldman-Rakic, PS ( 1990 ) Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys . Neurobiol Aging 11: 583 – 590 .

Google Scholar Crossref | Medline

Arnsten, AF, Jin, LE ( 2012 ) Guanfacine for the treatment of cognitive disorders: A century of discoveries at Yale . Yale J Biol Med 85: 45 – 58 .

Google Scholar Medline

Arnsten, AF, Li, BM ( 2005 ) Neurobiology of executive functions: Catecholamine influences on prefrontal cortical functions . Biol Psychiatry 57: 1377 – 1384 .

Google Scholar Crossref | Medline | ISI

Arnsten, AF, Cai, JX, Goldman-Rakic, PS ( 1988 ) The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: Evidence for alpha-2 receptor subtypes . J Neurosci 8: 4287 – 4298 .

Google Scholar Crossref | Medline | ISI

Aston-Jones, G, Cohen, JD ( 2005 ) Adaptive gain and the role of the locus coeruleus-norepinephrine system in optimal performance . J Comp Neurol 493: 99 – 110 .

Google Scholar Crossref | Medline | ISI

Aston-Jones, G, Gold, JI ( 2009 ) How we say no: Norepinephrine, inferior frontal gyrus, and response inhibition . Biol Psychiatry 65: 548 – 549 .

Google Scholar Crossref | Medline

Bari, A, Mar, AC, Theobald, DE. ( 2011 ) Prefrontal and monoaminergic contributions to stop-signal task performance in rats . J Neurosci 31: 9254 – 9263 .

Google Scholar Crossref | Medline | ISI

Bari, A, Robbins, TW ( 2013 ) Inhibition and impulsivity: Behavioral and neural basis of response control . Prog Neurobiol 108: 44 – 79 .

Google Scholar Crossref | Medline | ISI

Barry, D, Bates, ME, Labouvie, E ( 2008 ) FAS and CFL forms of verbal fluency differ in difficulty: A meta-analytic study . Appl Neuropsychol 15: 97 – 106 .

Google Scholar Crossref | Medline

Bearn, J, Gossop, M, Strang, J ( 1996 ) Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal . Drug Alcohol Depend 43: 87 – 91 .

Google Scholar Crossref | Medline

Begeer, S, Wierda, M, Scheeren, AM. ( 2014 ) Verbal fluency in children with autism spectrum disorders: Clustering and switching strategies . Autism 18: 1014 - 1018 .

Google Scholar SAGE Journals

Benton, AL ( 1968 ) Differential behavioural effects in frontal lobe disease . Neuropsychologia: 455 – 461 .

Google Scholar

Beversdorf, DQ, White, DM, Chever, DC. ( 2002 ) Central beta-adrenergic modulation of cognitive flexibility . Neuroreport 13: 2505 – 2507 .

Google Scholar Crossref | Medline | ISI

Billieux, J, Lagrange, G, Van der Linden, M. ( 2012 ) Investigation of impulsivity in a sample of treatment-seeking pathological gamblers: A multidimensional perspective . Psychiatry Res 198: 291 – 296 .

Google Scholar Crossref | Medline

Bissonette, GB, Martins, GJ, Franz, TM. ( 2008 ) Double dissociation of the effects of medial and orbital prefrontal cortical lesions on attentional and affective shifts in mice . J Neurosci 28: 11124 – 11130 .

Google Scholar Crossref | Medline | ISI

Blume, AW, Marlatt, GA ( 2009 ) The role of executive cognitive functions in changing substance use: What we know and what we need to know . Ann Behav Med 37: 117 – 125 .

Google Scholar Crossref | Medline | ISI

Bolla, KI, Lindgren, KN, Bonaccorsy, C. ( 1990 ) Predictors of verbal fluency (FAS) in the healthy elderly . J Clin Psychol 46: 623 – 628 .

Google Scholar Crossref | Medline

Brevers, D, Cleeremans, A, Verbruggen, F. ( 2012 ) Impulsive action but not impulsive choice determines problem gambling severity . PLoS One 7: e50647 .

Google Scholar Crossref | Medline

Brewer, JA, Worhunsky, PD, Carroll, KM. ( 2008 ) Pretreatment brain activation during Stroop task is associated with outcomes in cocaine-dependent patients . Biol Psychiatry 64: 998 – 1004 .

Google Scholar Crossref | Medline | ISI

Carroll, KM, Kiluk, BD, Nich, C. ( 2011 ) Cognitive function and treatment response in a randomized clinical trial of computer-based training in cognitive-behavioral therapy . Subst Use Misuse 46: 23 – 34 .

Google Scholar Crossref | Medline

Cecchi, M, Khoshbouei, H, Morilak, DA ( 2002 ) Modulatory effects of norepinephrine, acting on alpha 1 receptors in the central nucleus of the amygdala, on behavioral and neuroendocrine responses to acute immobilization stress . Neuropharmacology 43: 1139 – 1147 .

Google Scholar Crossref | Medline

Champod, AS, Petrides, M ( 2007 ) Dissociable roles of the posterior parietal and the prefrontal cortex in manipulation and monitoring processes . Proc Natl Acad Sci U S A 104: 14837 – 14842 .

Google Scholar Crossref | Medline

Chappell, PB, Riddle, MA, Scahill, L. ( 1995 ) Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette’s syndrome: Preliminary clinical experience . J Am Acad Child Adolesc Psychiatry 34: 1140 – 1146 .

Google Scholar Crossref | Medline | ISI

Childress, AC ( 2012 ) Guanfacine extended release as adjunctive therapy to psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder . Adv Ther 29: 385 – 400 .

Google Scholar Crossref | Medline | ISI

Clerkin, SM, Schulz, KP, Halperin, JM. ( 2009 ) Guanfacine potentiates the activation of prefrontal cortex evoked by warning signals . Biol Psychiatry 66: 307 – 312 .

Google Scholar Crossref | Medline

Colzato, LS, Huizinga, M, Hommel, B ( 2009 ) Recreational cocaine polydrug use impairs cognitive flexibility but not working memory . Psychopharmacology (Berl) 207: 225 – 234 .

Google Scholar Crossref | Medline

Colzato, LS, van den Wildenberg, WP, Hommel, B ( 2007 ) Impaired inhibitory control in recreational cocaine users . PLoS One 2: e1143 .

Google Scholar Crossref | Medline | ISI

Cools, R, Barker, RA, Sahakian, BJ. ( 2001 ) Mechanisms of cognitive set flexibility in Parkinson’s disease . Brain 124: 2503 – 2512 .

Google Scholar Crossref | Medline | ISI

De Oliveira, LG, Barroso, LP, Silveira, CM. ( 2009 ) Neuropsychological assessment of current and past crack cocaine users . Subst Use Misuse 44: 1941 – 1957 .

Google Scholar Crossref | Medline

Decamp, E, Clark, K, Schneider, JS ( 2011 ) Effects of the alpha-2 adrenoceptor agonist guanfacine on attention and working memory in aged non-human primates . Eur J Neurosci 34: 1018 – 1022 .

Google Scholar Crossref | Medline

Diana, M ( 2011 ) The dopamine hypothesis of drug addiction and its potential therapeutic value . Front Psychiatry 2: 64 .

Google Scholar Crossref | Medline

Dias, R, Robbins, TW, Roberts, AC ( 1996 ) Primate analogue of the Wisconsin Card Sorting Test: Effects of excitotoxic lesions of the prefrontal cortex in the marmoset . Behav Neurosci 110: 872 – 886 .

Google Scholar Crossref | Medline | ISI

Eagle, DM, Bari, A, Robbins, TW ( 2008 ) The neuropsychopharmacology of action inhibition: Cross-species translation of the stop-signal and go/no-go tasks . Psychopharmacology (Berl) 199: 439 – 456 .

Google Scholar Crossref | Medline | ISI

Engberg, G, Eriksson, E ( 1991 ). Effects of alpha2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats . Naunyn Schmiedebergs Arch Pharmacol. 343: 472 – 7 .

Google Scholar Crossref | Medline

Erb, S, Hitchcott, PK, Rajabi, H. ( 2000 ) Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking . Neuropsychopharmacology 23: 138 – 150 .

Google Scholar Crossref | Medline

Erb, S, Shaham, Y, Stewart, J ( 1998 ) The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats . J Neurosci 18: 5529 – 5536 .

Google Scholar Medline

Faraone, SV, Biederman, J, Spencer, T. ( 2005 ) Efficacy of atomoxetine in adult attention-deficit/hyperactivity disorder: A drug-placebo response curve analysis . Behav Brain Funct 1: 16 .

Google Scholar Crossref | Medline

Fassbender, C, Murphy, K, Foxe, JJ. ( 2004 ) A topography of executive functions and their interactions revealed by functional magnetic resonance imaging . Brain Res Cogn Brain Res 20: 132 – 143 .

Google Scholar Crossref | Medline

Fernandez-Serrano, MJ, Perez-Garcia, M, Perales, JC. ( 2010 ) Prevalence of executive dysfunction in cocaine, heroin and alcohol users enrolled in therapeutic communities . Eur J Pharmacol 626: 104 – 112 .

Google Scholar Crossref | Medline

Fillmore, MT, Rush, CR ( 2002 ) Impaired inhibitory control of behavior in chronic cocaine users . Drug Alcohol Depend 66: 265 – 273 .

Google Scholar Crossref | Medline | ISI

First, M, Spitzer, R, Gibbon, M. ( 1995 ) Structured Clinical Interview for DSM-IV. Patient Edition. Washington DC : American Psychiatric Press Inc .

Google Scholar

Fishbein, DH, Herman-Stahl, M, Eldreth, D. ( 2006 ) Mediators of the stress-substance-use relationship in urban male adolescents . Prev Sci 7: 113 – 126 .

Google Scholar Crossref | Medline | ISI

Fox, HC, Axelrod, SR, Paliwal, P. ( 2007a ) Difficulties in emotion regulation and impulse control during cocaine abstinence . Drug Alcohol Depend 89: 298 – 301 .

Google Scholar Crossref | Medline

Fox, HC, Bergquist, KL, Hong, KI. ( 2007b ) Stress-induced and alcohol cue-induced craving in recently abstinent alcohol-dependent individuals . Alcohol Clin Exp Res 31: 395 – 403 .

Google Scholar Crossref | Medline | ISI

Fox, HC, Morgan, PT, Sinha, R ( 2014 ) Sex differences in guanfacine effects on drug craving and stress arousal in cocaine-dependent individuals . Neuropsychopharmacology 39: 1527 – 1537 .

Google Scholar Crossref | Medline

Fox, HC, Seo, D, Tuit, K. ( 2012 ) Guanfacine effects on stress, drug craving and prefrontal activation in cocaine dependent individuals: preliminary findings . J Psychopharmacol 26: 958 – 972 .

Google Scholar SAGE Journals | ISI

Garavan, H, Hester, R ( 2007 ) The role of cognitive control in cocaine dependence . Neuropsychol Rev 17: 337 – 345 .

Google Scholar Crossref | Medline | ISI

Gau, SS, Shang, CY ( 2010 ) Improvement of executive functions in boys with attention deficit hyperactivity disorder: An open-label follow-up study with once-daily atomoxetine . Int J Neuropsychopharmacol 13: 243 – 256 .

Google Scholar Crossref | Medline | ISI

Gish, EC, Miller, JL, Honey, BL. ( 2010 ) Lofexidine, an {alpha}2-receptor agonist for opioid detoxification . Ann Pharmacother 44: 343 – 351 .

Google Scholar SAGE Journals

Golden, CJ ( 1975 ) A group version of the Stroop Color and Word Test . J Pers Assess 39: 386 – 388 .

Google Scholar Crossref | Medline

Gonzalez, G, Sevarino, K, Sofuoglu, M. ( 2003 ) Tiagabine increases cocaine-free urines in cocaine-dependent methadone-treated patients: Results of a randomized pilot study . Addiction 98: 1625 – 1632 .

Google Scholar Crossref | Medline

Hampshire, A, Owen, AM ( 2006 ) Fractionating attentional control using event-related fMRI . Cereb Cortex 16: 1679 – 1689 .

Google Scholar Crossref | Medline | ISI

Haney, M, Gunderson, EW, Jiang, H. ( 2010 ) Cocaine-specific antibodies blunt the subjective effects of smoked cocaine in humans . Biol Psychiatry 67: 59 – 65 .

Google Scholar Crossref | Medline | ISI

Hester, R, D’Esposito, M, Cole, MW. ( 2007 ) Neural mechanisms for response selection: Comparing selection of responses and items from working memory . Neuroimage 34: 446 – 454 .

Google Scholar Crossref | Medline

Hester, RL, Murphy, K, Foxe, JJ. ( 2004 ) Predicting success: Patterns of cortical activation and deactivation prior to response inhibition . J Cogn Neurosci 16: 776 – 785 .

Google Scholar Crossref | Medline

Higgins, ST, Alessi, SM, Dantona, RL ( 2002 ) Voucher-based incentives. A substance abuse treatment innovation . Addict Behav 27: 887 – 910 .

Google Scholar Crossref | Medline

Hunt, RD, Arnsten, AF, Asbell, MD ( 1995 ) An open trial of guanfacine in the treatment of attention-deficit hyperactivity disorder . J Am Acad Child Adolesc Psychiatry 34: 50 – 54 .

Google Scholar Crossref | Medline | ISI

Ijff, DM, Aldenkamp, AP ( 2013 ) Cognitive side-effects of antiepileptic drugs in children . Handb Clin Neurol 111: 707 – 718 .

Google Scholar Crossref | Medline

Jakala, P, Riekkinen, M, Sirvio, J. ( 1999a ) Guanfacine, but not clonidine, improves planning and working memory performance in humans . Neuropsychopharmacology 20: 460 – 470 .

Google Scholar Crossref | Medline | ISI

Jakala, P, Riekkinen, M, Sirvio, J. ( 1999b ) Clonidine, but not guanfacine, impairs choice reaction time performance in young healthy volunteers . Neuropsychopharmacology 21: 495 – 502 .

Google Scholar Crossref | Medline | ISI

Jarrott, B, Louis, WJ, Summers, RJ ( 1982 ) [3H]-guanfacine: A radioligand that selectively labels high affinity alpha2-adrenoceptor sites in homogenates of rat brain . Br J Pharmacol 75: 401 – 408 .

Google Scholar Crossref | Medline

Ji, XH, Ji, JZ, Zhang, H. ( 2008 ) Stimulation of alpha2-adrenoceptors suppresses excitatory synaptic transmission in the medial prefrontal cortex of rat . Neuropsychopharmacology 33: 2263 – 2271 .

Google Scholar Crossref | Medline

Kampman, KM, Pettinati, HM, Volpicelli, JR. ( 2004 ) Cocaine dependence severity predicts outcome in outpatient detoxification from cocaine and alcohol . Am J Addict 13: 74 – 82 .

Google Scholar Crossref | Medline

Kampman, KM, Volpicelli, JR, Mulvaney, F. ( 2002 ) Cocaine withdrawal severity and urine toxicology results from treatment entry predict outcome in medication trials for cocaine dependence . Addict Behav 27: 251 – 260 .

Google Scholar Crossref | Medline

Kang, SY, Kleinman, PH, Woody, GE. ( 1991 ) Outcomes for cocaine abusers after once-a-week psychosocial therapy . Am J Psychiatry 148: 630 – 635 .

Google Scholar Crossref | Medline | ISI

Kelley, BJ, Yeager, KR, Pepper, TH. ( 2007 ) The effect of propranolol on cognitive flexibility and memory in acute cocaine withdrawal . Neurocase 13: 320 – 327 .

Google Scholar Crossref | Medline

Kenemans, JL, Bekker, EM, Lijffijt, M. ( 2005 ) Attention deficit and impulsivity: Selecting, shifting, and stopping . Int J Psychophysiol 58: 59 – 70 .

Google Scholar Crossref | Medline

Le, AD, Funk, D, Juzytsch, W. ( 2011 ) Effect of prazosin and guanfacine on stress-induced reinstatement of alcohol and food seeking in rats . Psychopharmacology (Berl) 218: 89 – 99 .

Google Scholar Crossref | Medline

Li, CS, Milivojevic, V, Kemp, K. ( 2006 ) Performance monitoring and stop signal inhibition in abstinent patients with cocaine dependence . Drug Alcohol Depend 85: 205 – 212 .

Google Scholar Crossref | Medline

Logan, GD, Cowan, WB, Davis, KA ( 1984 ) On the ability to inhibit simple and choice reaction time responses: A model and a method . J Exp Psychol Hum Percept Perform 10: 276 – 291 .

Google Scholar Crossref | Medline | ISI

Lorea, I, Fernandez-Montalvo, J, Tirapu-Ustarroz, J. ( 2010 ) [Neuropsychological performance in cocaine addiction: A critical review] . Rev Neurol 51: 412 – 426 .

Google Scholar Medline

MacDonald, E, Kobilka, BK, Scheinin, M ( 1997 ) Gene targeting – homing in on alpha 2-adrenoceptor-subtype function . Trends Pharmacol Sci 18: 211 – 219 .

Google Scholar Crossref | Medline

McNair, DM, Lorr, M, Droppelman, LF ( 1971 ) Manual for the Profile of Mood States. San Diego : Educational and industrial Testing Service .

Google Scholar

Mercer, DE, Woody, GE ( 1999 ) Therapy Manuals for Drug Addiction Series: Individual Drug Counseling. Maryland : US Department of Health and Human Services . NIH Pub. No. 99 – 4380 .

Google Scholar

Mischel, W ( 2004 ) Toward an integrative science of the person . Annu Rev Psychol 55: 1 – 22 .

Google Scholar Crossref | Medline

Mosqueda-Garcia, R ( 1990 ) Guanfacine: A second generation alpha 2-adrenergic blocker . Am J Med Sci 299: 73 – 76 .

Google Scholar Crossref | Medline

Naifeh, JA, Tull, MT, Gratz, KL ( 2012 ) Anxiety sensitivity, emotional avoidance, and PTSD symptom severity among crack/cocaine dependent patients in residential treatment . Cognit Ther Res 36: 247 – 257 .

Google Scholar Crossref | Medline

Nigg, JT ( 2001 ) Is ADHD a disinhibitory disorder? Psychol Bull 127: 571 – 598 .

Google Scholar Crossref | Medline

Nigg, JT, Silk, KR, Stavro, G. ( 2005 ) Disinhibition and borderline personality disorder . Dev Psychopathol 17: 1129 – 1149 .

Google Scholar Crossref | Medline

O’Brien, MS, Anthony, JC ( 2005 ) Risk of becoming cocaine dependent: Epidemiological estimates for the United States, 2000–2001 . Neuropsychopharmacology 30: 1006 – 1018 .

Google Scholar Crossref | Medline

O’Leary, TA, Rohsenow, DJ, Martin, R. ( 2000 ) The relationship between anxiety levels and outcome of cocaine abuse treatment . Am J Drug Alcohol Abuse 26: 179 – 194 .

Google Scholar Crossref | Medline

Rama, P, Linnankoski, I, Tanila, H. ( 1996 ) Medetomidine, atipamezole, and guanfacine in delayed response performance of aged monkeys . Pharmacol Biochem Behav 55: 415 – 422 .

Google Scholar Crossref | Medline

Ramanujam, VM, Anderson, KE, Grady, JJ. ( 2011 ) Riboflavin as an oral tracer for monitoring compliance in clinical research . Open Biomark J 2011: 1 – 7 .

Google Scholar Crossref | Medline

Rey, A ( 1964 ) L’examinen clinique en psychologie. Paris : Presses Universitaires de France .

Google Scholar

Roberts, DC ( 2005 ) Preclinical evidence for GABAB agonists as a pharmacotherapy for cocaine addiction . Physiol Behav 86: 18 – 20 .

Google Scholar Crossref | Medline

Roberts, DC, Brebner, K ( 2000 ) GABA modulation of cocaine self-administration . Ann N Y Acad Sci 909: 145 – 158 .

Google Scholar Crossref | Medline

Rodriguez-Jimenez, R, Avila, C, Jimenez-Arriero, MA. ( 2006 ) Impulsivity and sustained attention in pathological gamblers: Influence of childhood ADHD history . J Gambl Stud 22: 451 – 461 .

Google Scholar Crossref | Medline

Rogers, RD, Andrews, TC, Grasby, PM. ( 2000 ) Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans . J Cogn Neurosci 12: 142 – 162 .

Google Scholar Crossref | Medline

Sahakian, BJ, Morris, RG, Evenden, JL. ( 1988 ) A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson’s disease . Brain 111 ( Pt 3 ): 695 – 718 .

Google Scholar Crossref | Medline

Sallee, FR, Kollins, SH, Wigal, TL ( 2012 ) Efficacy of guanfacine extended release in the treatment of combined and inattentive only subtypes of attention-deficit/hyperactivity disorder . J Child Adolesc Psychopharmacol 22: 206 – 214 .

Google Scholar Crossref | Medline

Sanchez-Hervas, E, Llorente del Pozo, JM ( 2012 ) [Relapse in cocaine addiction: a review] . Adicciones 24: 269 – 279 .

Google Scholar Medline

Scahill, L, Chappell, PB, Kim, YS. ( 2001 ) A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder . Am J Psychiatry 158: 1067 – 1074 .

Google Scholar Crossref | Medline | ISI

Seedat, YK ( 1985 ) Clonidine and guanfacine – comparison of their effects on haemodynamics in hypertension . S Afr Med J 67: 557 – 559 .

Google Scholar Medline

Senderecka, M, Grabowska, A, Szewczyk, J. ( 2012 ) Response inhibition of children with ADHD in the stop-signal task: An event-related potential study . Int J Psychophysiol 85: 93 – 105 .

Google Scholar Crossref | Medline | ISI

Shaham, Y, Shalev, U, Lu, L. ( 2003 ) The reinstatement model of drug relapse: History, methodology and major findings . Psychopharmacology (Berl) 168: 3 – 20 .

Google Scholar Crossref | Medline | ISI

Shang, CY, Gau, SS ( 2012 ) Improving visual memory, attention, and school function with atomoxetine in boys with attention-deficit/hyperactivity disorder . J Child Adolesc Psychopharmacol 22: 353 – 363 .

Google Scholar Crossref | Medline | ISI

Shields, AD, Wang, Q, Winder, DG ( 2009 ) Alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis . Neuroscience 163: 339 – 351 .

Google Scholar Crossref | Medline | ISI

Sinha, R ( 2001 ) How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl) 158: 343 – 359 .

Google Scholar Crossref | Medline | ISI

Sinha, R, Fox, HC, Hong, KA. ( 2009 ) Enhanced negative emotion and alcohol craving, and altered physiological responses following stress and cue exposure in alcohol dependent individuals . Neuropsychopharmacology 34: 1198 – 1208 .

Google Scholar Crossref | Medline | ISI

Sinha, R, Fox, HC, Hong, KI. ( 2011 ) Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes . Arch Gen Psychiatry 68: 942 – 952 .

Google Scholar Crossref | Medline

Soar, K, Mason, C, Potton, A. ( 2012 ) Neuropsychological effects associated with recreational cocaine use . Psychopharmacology (Berl) 222: 633 – 643 .

Google Scholar Crossref | Medline

Sofuoglu, M, DeVito, EE, Waters, AJ. ( 2013 ) Cognitive enhancement as a treatment for drug addictions . Neuropharmacology 64: 452 – 463 .

Google Scholar Crossref | Medline | ISI

Sommer, BR, Mitchell, EL, Wroolie, TE. ( 2013 ) Topiramate: Effects on cognition in patients with epilepsy, migraine headache and obesity . Ther Adv Neurol Disord 6: 211 – 227 .

Google Scholar SAGE Journals | ISI

Sorkin, EM, Heel, RC ( 1986 ) Guanfacine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of hypertension . Drugs 31: 301 – 336 .

Google Scholar Crossref | Medline

Streeter, CC, Terhune, DB, Whitfield, TH. ( 2008 ) Performance on the Stroop predicts treatment compliance in cocaine-dependent individuals . Neuropsychopharmacology 33: 827 – 836 .

Google Scholar Crossref | Medline | ISI

Summers, RJ, Jarrott, B, Louis, WJ ( 1981 ) Comparison of [3H]clonidine and [3H]guanfacine binding to alpha 2 adrenoceptors in membranes from rat cerebral cortex . Neurosci Lett 25: 31 – 36 .

Google Scholar Crossref | Medline

Swann, NC, Tandon, N, Pieters, TA. ( 2013 ) Intracranial electroencephalography reveals different temporal profiles for dorsal- and ventro-lateral prefrontal cortex in preparing to stop action . Cereb Cortex 23: 2479 – 2488 .

Google Scholar Crossref | Medline

Swartz, BE, McDonald, CR, Patel, A. ( 2008 ) The effects of guanfacine on working memory performance in patients with localization-related epilepsy and healthy controls . Clin Neuropharmacol 31: 251 – 260 .

Google Scholar Crossref | Medline | ISI

Thanos, PK, Taintor, NB, Rivera, SN. ( 2004 ) DRD2 gene transfer into the nucleus accumbens core of the alcohol preferring and nonpreferring rats attenuates alcohol drinking . Alcohol Clin Exp Res 28: 720 – 728 .

Google Scholar Crossref | Medline

Tice, DM, Bratslavsky, E, Baumeister, RF ( 2001 ) Emotional distress regulation takes precedence over impulse control: If you feel bad, do it! J Pers Soc Psychol 80: 53 – 67 .

Google Scholar Crossref | Medline

Troyer, AK, Moscovitch, M, Winocur, G ( 1997 ) Clustering and switching as two components of verbal fluency: Evidence from younger and older healthy adults . Neuropsychology 11: 138 – 146 .

Google Scholar Crossref | Medline | ISI

Troyer, AK, Moscovitch, M, Winocur, G. ( 1998 ) Clustering and switching on verbal fluency tests in Alzheimer’s and Parkinson’s disease . J Int Neuropsychol Soc 4: 137 – 143 .

Google Scholar Crossref | Medline

Turner, MA ( 1999 ) Generating novel ideas: Fluency performance in high-functioning and learning disabled individuals with autism . J Child Psychol Psychiatry 40: 189 – 201 .

Google Scholar Crossref | Medline

Turner, TH, LaRowe, S, Horner, MD. ( 2009 ) Measures of cognitive functioning as predictors of treatment outcome for cocaine dependence . J Subst Abuse Treat 37: 328 – 334 .

Google Scholar Crossref | Medline | ISI

van Holst, RJ, Schilt, T ( 2011 ) Drug-related decrease in neuropsychological functions of abstinent drug users . Curr Drug Abuse Rev 4: 42 – 56 .

Google Scholar Crossref | Medline

Verdejo-Garcia, A, Perez-Garcia, M ( 2007 ) Profile of executive deficits in cocaine and heroin polysubstance users: Common and differential effects on separate executive components . Psychopharmacology (Berl) 190: 517 – 530 .

Google Scholar Crossref | Medline

Verdejo-Garcia, A, Betanzos-Espinosa, P, Lozano, OM. ( 2012 ) Self-regulation and treatment retention in cocaine dependent individuals: A longitudinal study . Drug Alcohol Depend 122: 142 – 148 .

Google Scholar Crossref | Medline | ISI

Verrico, CD, Haile, CN, Newton, TF. ( 2013 ) Pharmacotherapeutics for substance-use disorders: A focus on dopaminergic medications . Expert Opin Investig Drugs.

Google Scholar Crossref | Medline

Vitkovitch, M, Bishop, S, Dancey, C. ( 2002 ) Stroop interference and negative priming in patients with multiple sclerosis . Neuropsychologia 40: 1570 – 1576 .

Google Scholar Crossref | Medline

Wang, M, Ramos, BP, Paspalas, CD. ( 2007 ) Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex . Cell 129: 397 – 410 .

Google Scholar Crossref | Medline | ISI