Abstract
Rationale
Most studies of the reinforcing effects of stimulants have focused on the drugs’ capacity to induce positive mood (i.e., euphoria). However, recent findings suggest drugs may also alter emotional reactivity to external stimuli, and that this may occur independently of direct effects on mood.
Objectives
We aimed to examine effects of d-amphetamine, a prototypic stimulant, on self-reported and psychophysiological reactivity to emotional stimuli as well as overall subjective mood. We predicted that amphetamine would enhance reactivity to pleasant stimuli, particularly, stimuli with social content and that these effects would be independent of the drug’s direct effects on mood.
Methods
Over three sessions, 36 healthy normal adults received placebo, d-amphetamine 10 and 20 mg under counterbalanced double-blind conditions. At each session, emotional reactivity to standardized positive, neutral, and negative pictures with and without social content was measured in self-reports and facial muscles sensitive to emotional state. Drug effects on cardiovascular variables and subjective mood were also measured.
Results
Amphetamine produced euphoria, feelings of drug effect, and increased blood pressure. Most notably, amphetamine enhanced self-reported positive reactions to all pictures and psychophysiological reactions to positive pictures. These effects were not significantly related to drug-induced mood changes. Contrary to our hypothesis, effects of amphetamine on emotional reactivity were not moderated by social content.
Conclusions
This study demonstrates a previously unexamined and potentially reinforcing effect of stimulant drugs in humans, distinct from more typically measured euphorigenic effects, and suggests new areas of research in stimulant abuse risk and adaptations occurring during drug dependence.
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Notes
IAPS numbers for each subset, followed by IAPS normative mean valence (V, 1 = extremely unpleasant–9 = extremely pleasant) and arousal (A, 1 = extremely unarousing–9 = extremely arousing) ratings: Set 1 social/negative = 6,022, 9,421, 2,053, 9,424, 4,621, 9,584, 2,694, 9,045, 9,594, V = 3.03, A = 5.13; Set 1 nonsocial/negative = 9,560, 9,911, 9,320, 9,180, 1,274, 9,373, 7,360, 1,280, 9,010, V = 3.08, A = 5.08; Set 1 social/neutral = 2,272, 9,700, 2,704, 2,595, 2,397, 2,580, 7,620, V = 5.15, A = 3.86; Set 1 nonsocial/neutral = 7,211, 1,935, 7,055, 7,233, 7,207, 5,920, 7,182, 7,830, 7,285, V = 5.12, A = 4.00; Set 1 social/positive = 4,598, 8,467, 8,600, 8,116, 4,601, 2,391, 2,216, 7,502, 8,420, V = 6.99, A = 5.32; Set 1 nonsocial/positive = 1,640, 7,352, 5,991, 7,410, 5,450, 7,508, 5,260, 5,700, 8,170, V = 6.94, 5.20; Set 2 social/negative = 9,420, 9,903, 6,838, 2,700, 6,562, 3,216, 2,312, 3,280, 9,926, V = 3.12, A = 5.18; Set 2 nonsocial/negative = 9,301, 7,380, 9,561, 9,630, 9,621, 1,111, 1,220, 9,440, 9,390, V = 3.07, A = 5.25; Set 2 social/neutral = 8,010, 3,210, 8,475, 2,393, 4,605, 2,485, 2,593, 2,606, 7,496, V = 5.28, A = 4.40; Set 2 nonsocial/neutral = 9,472, 7,054, 5,510, 1,616, 7,242, 7,500, 5,395, 7,283, 5,661, V = 5.11, A = 3.81; Set 2 social/positive = 2,594, 4,625, 9,156, 8,371, 2,373, 4,599, 2,345, 8,210, 8,496, V = 6.92, A = 5.24; Set 2 nonsocial/positive = 7,289, 7,450, 1,660, 5,849, 8,500, 1,540, 5,660, 7,270, 5,480, V = 6.92, A = 5.12; Set 3 social/negative = 6,212, 2,141, 9,425, 2,455, 2,691, 6,561, 6,836, 2,718, 4,635, V = 3.04, A = 5.15; Set 3 nonsocial/negative = 9,140, 9,300, 9,620, 9,290, 9,470, 9,471, 9,008, 9,480, 9,110, V = 3.00, A = 5.05; Set 3 social/neutral = 2,695, 9,582, 9,913, 9,411, 4,000, 2,396, 2,850, 2,579, 2,435, V = 4.84, A = 4.18; Set 3 nonsocial/neutral = 5,120, 7,590, 7,037, 7,100, 7,546, 7,190, 7,183, 1,313, 1,947, V = 5.25, A = 3.73; Set 3 social/positive = 2,605, 4,606, 2,358, 2,344, 4,624, 4,650, 2,352, 4,626, 8,499, V = 6.93, A = 5.14; Set 3 nonsocial/positive = 1,661, 7,284, 7,481, 8,162, 8,531, 7,480, 7,260, 8,502, 5,600, V = 6.92, A = 4.89.
References
Barr RS, Pizzagalli DA, Culhane MA, Goff DC, Evins AE (2008) A single dose of nicotine enhances reward responsiveness in nonsmokers: implications for development of dependence. Biol Psychiatry 63:1061–1065. doi:10.1016/j.biopsych.2007.09.015
Boys A, Marsden J, Strang J (2001) Understanding reasons for drug use amongst young people: a functional perspective. Health Educ Res 16:457. doi:10.1093/her/16.4.457
Britton JC, Phan KL, Taylor SF, Welsh RC, Berridge KC, Liberzon I (2006a) Neural correlates of social and nonsocial emotions: an fMRI study. NeuroImage 31:397–409. doi:10.1016/j.neuroimage.2005.11.027
Britton JC, Taylor SF, Berridge KC, Mikels JA, Liberzon I (2006b) Differential subjective and psychophysiological responses to socially and nonsocially generated emotional stimuli. Emotion 6:150–155. doi:10.1037/1528-3542.6.1.150
Cacioppo JT, Norris CJ, Decety J, Monteleone G, Nusbaum H (2009) In the eye of the beholder: individual differences in perceived social isolation predict regional brain activation to social stimuli. J Cogn Neurosci 21:83–92. doi:10.1162/jocn.2009.21007
Cador M, Taylor JR, Robbins TW (1991) Potentiation of the effects of reward-related stimuli by dopaminergic-dependent mechanisms in the nucleus accumbens. Psychopharmacology (Berl) 104:377–385. doi:10.1007/bf02246039
Caggiula AR, Donny EC, Palmatier MI, Liu X, Chaudhri N, Sved AF, Bevins RA (2009) The role of nicotine in smoking: a dual-reinforcement model. In: Bevins RA, Caggiula AR (eds) The motivational impact of nicotine and its role in tobacco use. Nebraska symposium on motivation. Springer Science and Business Media, New York, pp 91–109
Chait LD, Fischman MW, Schuster CR (1985) “Hangover” effects the morning after marijuana smoking. Drug Alcohol Depend 15:229–238. doi:10.1016/0376-8716(85)90002-x
Cinciripini PM, Robinson JD, Carter BL, Lam C, Wu X, de Moor CA, Baile WF, Wetter DW (2006) The effects of smoking deprivation and nicotine administration on emotional reactivity. Nicotine Tobacco Res 8:379–392. doi:10.1080/14622200600670272
Davidson RJ (1998) Affective style and affective disorders: perspectives from affective neuroscience. Cogn Emotion 12:307–330. doi:10.1080/026999398379628
Dawkins L, Powell JH, West R, Powell J, Pickering A (2006) A double-blind placebo controlled experimental study of nicotine: I. Effects on incentive motivation. Psychopharmacology (Berl) 189:355–367. doi:10.1007/s00213-006-0588-8
de Wit H, Uhlenhuth EH, Johanson CE (1986) Individual differences in the reinforcing and subjective effects of amphetamine and diazepam. Drug Alcohol Depend 16:341–360. doi:10.1016/0376-8716(86)90068-2
Dimberg U, Thunberg M, Elmehed K (2000) Unconscious facial reactions to emotional facial expressions. Psychol Sci 11:86–89. doi:10.1111/1467-9280.00221
Dimberg U, Thunberg M, Grunedal S (2002) Facial reactions to emotional stimuli: automatically controlled emotional responses. Cogn Emotion 16:449–472. doi:10.1080/02699930143000356
Donohue KF, Curtin JJ, Patrick CJ, Lang AR (2007) Intoxication level and emotional response. Emotion 7:103–112. doi:10.1037/1528-3542.7.1.103
Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489. doi:10.1038/nn1579
First MB, Spitzer RL, Gibbon M, Williams JB (1996) Strutured clinical interview for DSM-IV axis I disorders. Biometrics Research Department, New York
Fischman MW, Foltin RW (1991) Utility of subjective-effects measurements in assessing abuse liability of drugs in humans. Br J Addict 86:1563–1570. doi:10.1111/j.1360-0443.1991.tb01749.x
Frohmader KS, Pitchers KK, Balfour ME, Coolen LM (2009) Mixing pleasures: review of the effects of drugs on sex behavior in humans and animal models. Horm Behav 58:149–162. doi:10.1016/j.yhbeh.2009.11.009
Gabbay FH (2003) Variations in affect following amphetamine and placebo: markers of stimulant drug preference. Exp Clin Psychopharmacol 11:91–101. doi:10.1037/1064-1297.11.1.91
Gospic K, Gunnarsson T, Fransson P, Ingvar M, Lindefors N, Petrovic P (2008) Emotional perception modulated by an opioid and a cholecystokinin agonist. Psychopharmacology (Berl) 197:295–307. doi:10.1007/s00213-007-1032-4
Gros DF, Hawk LW Jr, Moscovitch DA (2009) The psychophysiology of social anxiety: emotional modulation of the startle reflex during socially-relevant and-irrelevant pictures. Int J Psychophysiol 73:207–211. doi:10.1016/j.ijpsycho.2009.03.001
Harmer CJ, Bhagwagar Z, Perrett DI, Völlm BA, Cowen PJ, Goodwin GM (2003) Acute SSRI administration affects the processing of social cues in healthy volunteers. Neuropsychopharmacology 28:148–152. doi:10.1038/sj.npp.1300004
Harmer CJ, Heinzen J, O’Sullivan U, Ayres RA, Cowen PJ (2008) Dissociable effects of acute antidepressant drug administration on subjective and emotional processing measures in healthy volunteers. Psychopharmacology (Berl) 199:495–502. doi:10.1007/s00213-007-1058-7
Heinz A, Wrase J, Kahnt T, Beck A, Bromand Z, Grüsser SM, Kienast T, Smolka MN, Flor H, Mann K (2007) Brain activation elicited by affectively positive stimuli is associated with a lower risk of relapse in detoxified alcoholic subjects. Alcohol Clin Exp Res 31:1138–1147. doi:10.1111/j.1530-0277.2007.00406.x
Heishman SJ, Stitzer ML (1989) Effect of d-amphetamine, secobarbital, and marijuana on choice behavior: social versus nonsocial options. Psychopharmacology (Berl) 99:156–162. doi:10.1007/bf00442801
Higgins ST, Hughes JR, Bickel WK (1989) Effects of d-amphetamine on choice of social versus monetary reinforcement: a discrete-trial test. Pharmacol Biochem Behav 34:297–301. doi:10.1016/0091-3057(89)90315-8
Johanson CE, Uhlenhuth EH (1980) Drug preference and mood in humans: d-amphetamine. Psychopharmacology (Berl) 71:275–279. doi:10.1007/bf00433062
Judd CM, Kenny DA, McClelland GH (2001) Estimating and testing mediation and moderation in within-subject designs. Psychol Methods 6:115–134. doi:10.1037/1082-989x.6.2.115
Judd CM, McClelland GH, Ryan CS (2009) Data analysis: a model comparison approach, 2nd edn. Routledge/Taylor & Francis, New York
Kassel JD (2010) Substance abuse and emotion. APA Books, Washington, DC
Lang PJ, Bradley MM, Cuthbert BN (1999) International affective picture system (IAPS): technical manual and affective ratings. NIMH Center for the study of emotion and attention, University of Florida, Gainesville, FL
Lang PJ, Greenwald MK, Bradley MM, Hamm AO (1993) Looking at pictures: affective, facial, visceral, and behavioral reactions. Psychophysiology 30:261–273. doi:10.1111/j.1469-8986.1993.tb03352.x
Larsen JT, Norris CJ, Cacioppo JT (2003) Effects of positive and negative affect on electromyographic activity over zygomaticus major and corrugator supercilii. Psychophysiology 40:776–785. doi:10.1111/1469-8986.00078
Larsen JT, Norris CJ, McGraw AP, Hawkley LC, Cacioppo JT (2009) The evaluative space grid: a single-item measure of positivity and negativity. Cogn Emotion 23:453–480. doi:10.1080/02699930801994054
Leyton M, aan het Rot M, Booij L, Baker GB, Young SN, Benkelfat C (2007) Mood-elevating effects of d-amphetamine and incentive salience: the effect of acute dopamine precursor depletion. J Psychiatry Neurosci 32:129–136
Leyton M, Casey KF, Delaney JS, Kolivakis T, Benkelfat C (2005) Cocaine craving, euphoria, and self-administration: a preliminary study of the effect of catecholamine precursor depletion. Behav Neurosci 119:1619–1627. doi:10.1037/0735-7044.119.6.1619
Lubman DI, Allen NB, Peters LA, Deakin JFW (2008) Electrophysiological evidence that drug cues have greater salience than other affective stimuli in opiate addiction. J Psychopharmacol (Oxf) 22:836–842. doi:10.1177/0269881107083846
Lubman DI, Yücel M, Kettle JWL, Scaffidi A, MacKenzie T, Simmons JG, Allen NB (2009) Responsiveness to drug cues and natural rewards in opiate addiction: associations with later heroin use. Arch Gen Psychiatry 66:205–213. doi:10.1001/archgenpsychiatry.2008.522
Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic, subjective and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, an methylphenidate in man. Clin Pharmacol Ther 12:245–258
Muller D, Judd CM, Yzerbyt VY (2005) When moderation is mediated and mediation is moderated. J Pers Soc Psychol 89:852–863. doi:10.1037/0022-3514.89.6.852
Norbury R, Mackay CE, Cowen PJ, Goodwin GM, Harmer CJ (2008) The effects of reboxetine on emotional processing in healthy volunteers: an fMRI study. Mol Psychiatry 13:1011–1020. doi:10.1038/sj.mp.4002091
Patrick CJ, Berthot BD, Moore JD (1996) Diazepam blocks fear-potentiated startle in humans. J Abnorm Psychol 105:89–96. doi:10.1037/0021-843X.105.1.89
Robinson JD, Cinciripini PM, Carter BL, Lam CY, Wetter DW (2007) Facial EMG as an index of affective response to nicotine. Exp Clin Psychopharmacol 15:390–399. doi:10.1037/1064-1297.15.4.390
Rose JE, Behm FM, Westman EC, Johnson M (2000) Dissociating nicotine and nonnicotine components of cigarette smoking. Pharmacol Biochem Behav 67:71–81. doi:10.1016/S0091-3057(00)00301-4
Taylor JR, Robbins TW (1984) Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology (Berl) 84:405–412. doi:10.1007/bf00555222
Thiel KJ, Okun AC, Neisewander JL (2008) Social reward-conditioned place preference: a model revealing an interaction between cocaine and social context rewards in rats. Drug Alcohol Depend 96:202–212. doi:10.1016/j.drugalcdep.2008.02.013
Thiel KJ, Sanabria F, Neisewander JL (2009) Synergistic interaction between nicotine and social rewards in adolescent male rats. Psychopharmacology (Berl) 204:391–402. doi:10.1007/s00213-009-1470-2
White TL, Justice AJH, de Wit H (2002) Differential subjective effects of d-amphetamine by gender, hormone levels and menstrual cycle phase. Pharmacol Biochem Behav 73:729–741. doi:10.1016/s0091-3057(02)00818-3
Wise RA (1996) Addictive drugs and brain stimulation reward. Annu Rev Neurosci 19:319–340. doi:10.1146/annurev.ne.19.030196.001535
Acknowledgements
The authors thank Dr. John Cacioppo and his staff at the University of Chicago Center for Cognitive and Social Neuroscience for assistance with design and technical issues, and Cassandra Esposito, Celina Joos, and Megan Leino for their work on this study. The National Institute on Drug Abuse supported this work through grant R01 DA02812 to Dr. Harriet de Wit. Dr. Margaret Wardle is supported by a National Institute on Drug Abuse Training grant, T32 DA007255.
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Wardle, M.C., de Wit, H. Effects of amphetamine on reactivity to emotional stimuli. Psychopharmacology 220, 143–153 (2012). https://doi.org/10.1007/s00213-011-2498-7
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DOI: https://doi.org/10.1007/s00213-011-2498-7