Skip to main content

Advertisement

SpringerLink
Log in

High-dose MDMA does not result in long-term changes in impulsivity in the rat

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Evidence suggests that recreational users of (±)3,4-methylenedioxymethamphetamine HCl (MDMA, “ecstasy”) have cognitive and behavioral deficits and show increased impulsivity consistent with 5-hydroxytryptamine (5-HT) neurotoxicity. MDMA effects on impulsivity in users are difficult to establish being confounded by polydrug use and individual predisposition to impulsivity or behavioral inhibition.

Objective

We previously observed a long-term anxiolytic effect of a neurotoxic dose of MDMA on elevated plus maze behavior in Dark Agouti (DA) rats while other strains were reported to show anxiogenesis. We have now examined whether MDMA influences impulsivity producing disinhibited behavior interpretable as anxiolysis.

Methods

Impulsivity was measured using an operant visuospatial discrimination procedure. Male DA rats (n=24) were trained to lever press for food reward in response to a light-stimulus and subsequently required to withhold responding. Correct responses, premature responses, and response latencies were used as measures of accuracy and impulsivity. Trained rats were administered MDMA (5 mg/kg, i.p. at 3-h intervals to a total of three injections). Performance was measured at 3 h and 7, 27, 49, and 80 days posttreatment.

Results

There was a short-term effect of MDMA on the percentage of correct responses at 3 h and day 1 with recovery to control levels by days 7–8 and no significant long-term changes up to day 80. There was no effect of MDMA on premature responses on any of the days measured. MDMA reduced cortical 5-HT content (MDMA 363±14 ng/g and control 440±10 ng/g tissue).

Conclusion

These results suggest that impulsivity may not be directly altered by MDMA despite serotonergic neurotoxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Balogh B, Molnar E, Jakus R, Olverman HJ, Kelly PAT, Kantor S, Bagdy G (2004) Effects of a single dose of 3,4-methylenedioxymethamphetamine on circadian patterns, motor activity and sleep in drug-naive rats and rats previously exposed to MDMA. Psychopharmacology 173:296–309

    Article  PubMed  CAS  Google Scholar 

  • Battaglia G, Brooks BP, Kulsakdinum C, Desouza EB (1988) Pharmacologic profile of MDMA (3,4-Methylenedioxymethamphetamine) at various brain recognition sites. Eur J Pharmacol 149(1–2):159–163

    Article  PubMed  CAS  Google Scholar 

  • Bizot JC, Le Bihan C, Puech AJ, Hamon M, Thiebot MH (1999) Serotonin and tolerance to delay of reward in rats. Psychopharmacology 146:400–412

    Article  PubMed  CAS  Google Scholar 

  • Butler GKL, Montgomery AMJ (2004) Impulsivity, risk taking and recreational ‘ecstasy’ (MDMA) use. Drug Alcohol Depend 76:55–62

    Article  PubMed  CAS  Google Scholar 

  • Chudasama Y, Passetti F, Rhodes SEV, Lopian D, Desai A, Robbins TW (2003) Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity. Behav Brain Res 146:105–119

    Article  PubMed  CAS  Google Scholar 

  • Colado MI, O’Shea E, Green AR (2004) Acute and long-term effects of MDMA on cerebral dopamine biochemistry and function. Psychopharmacology 173:249–263

    Article  PubMed  CAS  Google Scholar 

  • Denk F, Walton ME, Jennings KA, Sharp T, Rushworth MFS, Bannerman DM (2005) Differential involvement of serotonin and dopamine systems in cost-benefit decisions about delay or effort. Psychopharmacology 179:587–596

    Article  PubMed  CAS  Google Scholar 

  • Gamma A, Brandeis D, Brandeis R, Vollenweider FX (2005) The P3 in ‘ecstasy’ polydrug users during response inhibition and execution. J Psychopharmacol 19:504–512

    Article  PubMed  Google Scholar 

  • Gerbing DW, Ahadi SA, Patton JH (1987) Toward a conceptualization of impulsivity—components across the behavioral and self-report domains. Multivariate Behav Res 22:357–379

    Article  Google Scholar 

  • Gouzoulis-Mayfrank E, Daumann J, Tuchtenhagen F, Pelz S, Becker S, Kunert HJ, Fimm B, Sass H (2000) Impaired cognitive performance in drug free users of recreational ecstasy (MDMA). J Neurol Neurosurg Psychiatry 68:719–725

    Article  PubMed  CAS  Google Scholar 

  • Green AR, McGregor IS (2002) On the anxiogenic and anxiolytic nature of long-term cerebral 5-HT depletion following MDMA. Psychopharmacology 164:448–450

    Article  CAS  Google Scholar 

  • Green AR, Mechan AO, Elliott JM, O’Shea E, Colado MI (2003) The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacol Rev 55:463–508

    Article  PubMed  CAS  Google Scholar 

  • Green AR, O’Shea E, Saadat KS, Elliott JM, Colado MI (2005) Studies on the effect of MDMA (‘ecstasy’) on the body temperature of rats housed at different ambient room temperatures Br J Pharmacol 146:306–312

    Article  PubMed  CAS  Google Scholar 

  • Halpern JH, Pope HG, Sherwood AR, Barry S, Hudson JI, Yurgelun-Todd D (2004) Residual neuropsychological effects of illicit 3,4-methylenedioxymethamphetamine (MDMA) in individuals with minimal exposure to other drugs. Drug Alcohol Depend 75:135–147

    Article  PubMed  CAS  Google Scholar 

  • Hanson KL, Luciana M (2004) Neurocognitive function in users of MDMA: the importance of clinically significant patterns of use. Psychol Med 34:229–246

    Article  PubMed  Google Scholar 

  • Malle BF, Neubauer AC (1991) Impulsivity, reflection, and questionnaire response latencies-no evidence for a broad impulsivity trait. Pers Individ Differ 12:865–871

    Article  Google Scholar 

  • McCann UD, Ridenour A, Shaham Y, Ricaurte GA (1994) Serotonin neurotoxicity after (±) 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)—a controlled study in humans. Neuropsychopharmacology 10:129–138

    PubMed  CAS  Google Scholar 

  • McCann UD, Szabo A, Scheffel U, Dannals RF, Ricaurte GA (1998) Neurotoxic effects in human brains after use of 3,4-methylenedioxymethamphetamine (“ecstasy”) viewed by positron emission tomography. Lancet 352:1433–1437

    Article  PubMed  CAS  Google Scholar 

  • McGregor IS, Clemens KJ, Van der Plasse G, Li KM, Hunt GE, Chen F, Lawrence AJ (2003) Increased anxiety 3 months after brief exposure to MDMA (‘ecstasy’) in rats: association with altered 5-HT transporter and receptor density. Neuropsychopharmacology 28:1472–1484

    Article  PubMed  CAS  Google Scholar 

  • Mechan AO, Moran PM, Elliott JM, Young AMJ, Joseph MH, Green AR (2002a) A study of the effect of a single neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) on the subsequent long-term behaviour of rats in the plus maze and open field. Psychopharmacology 159:167–175

    Article  PubMed  CAS  Google Scholar 

  • Mechan AO, Moran PM, Elliott JM, Young AMJ, Joseph MH, Green AR (2002b) A comparison between Dark Agouti and Sprague-Dawley rats in their behaviour on the elevated plus maze, open field apparatus and activity meters, and their response to diazepam. Psychopharmacology 159:188–195

    Article  PubMed  CAS  Google Scholar 

  • Moeller FG, Dougherty DM, Barratt ES, Schmitz JM, Swann AC, Grabowski J (2001) The impact of impulsivity on cocaine use and retention in treatment. J Subst Abuse Treat 21:193–198

    Article  PubMed  CAS  Google Scholar 

  • Morgan MJ (1998) Recreational use of “ecstasy” (MDMA) is associated with elevated impulsivity. Neuropsychopharmacology 19:252–264

    Article  PubMed  CAS  Google Scholar 

  • O’Shea E, Granados R, Esteban B, Colado MI, Green AR (1998). The relationship between the degree of neurodegeneration of rat brain 5-HT nerve terminals and the dose and frequency of administration of MDMA (‘ecstasy’). Neuropharmacology 37:919–926

    Article  PubMed  CAS  Google Scholar 

  • O’Shea E, Orio L, Escobedo I, Sanchez V, Camarero J, Green AR, Colado MI (2006) MDMA-induced neurotoxicity: long-term effects on 5-HT biosynthesis and the influence of ambient temperature Br J Pharmacol DOI 10.1038/sj.bjp.0706783

  • Parrott AC (2002) Recreational ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav 71:837–844

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC, Sisk E, Turner JJD (2000) Psychobiological problems in heavy ‘ecstasy’ (MDMA) polydrug users. Drug Alcohol Depend 60:105–110

    Article  PubMed  CAS  Google Scholar 

  • Petry NM (2001) Substance abuse, pathological gambling, and impulsiveness. Drug Alcohol Depend 63:29–38

    Article  PubMed  CAS  Google Scholar 

  • Piper BJ, Fraiman JB, Meyer JS (2005) Repeated MDMA (“ecstasy”) exposure in adolescent male rats alters temperature regulation, spontaneous motor activity, attention and serotonin transporter binding. Dev Psychobiol 47:145–157

    Article  PubMed  CAS  Google Scholar 

  • Rodgers J, Buchanan T, Scholey AB, Heffernan TM, Ling J, Parrott A (2001) Differential effects of Ecstasy and cannabis on self-reports of memory ability: a web-based study. Hum Psychopharmacol 16:619–625

    Article  PubMed  CAS  Google Scholar 

  • Schifano F, Di Furia L, Forza C, Minicuci N, Bricolo R (1998) MDMA (‘ecstasy’) consumption in the context of polydrug abuse: a report on 150 patients. Drug Alcohol Depend 52:85–90

    Article  PubMed  CAS  Google Scholar 

  • Schmidt CJ, Taylor VL (1987) Depression of rat-brain tryptophan-hydroxylase activity following the acute administration of methylenedioxymethamphetamine. Biochem Pharmacol 36(23):4095–4102

    Article  PubMed  CAS  Google Scholar 

  • Sher KJ, Trull TJ (1994) Personality and disinhibitory psychopathology-alcoholism and antisocial personality disorder. J Abnorm Psychol 103:92–102

    Article  PubMed  CAS  Google Scholar 

  • Sher KJ, Bartholow BD, Wood MD (2000) Personality and substance use disorders: a prospective study. J Consult Clin Psychol 68:818–829

    Article  PubMed  CAS  Google Scholar 

  • Semple SJ, Zians J, Grant I, Patterson TL (2005) Impulsivity and methamphetamine use. J Subst Abuse Treat 29:85–93

    Article  PubMed  Google Scholar 

  • Thomasius R, Petersen K, Buchert R, Andresen B, Zapletalova P, Wartberg L, Nebeling B, Schmoldt, A (2003) Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users. Psychopharmacology 167:85–96

    PubMed  CAS  Google Scholar 

  • Travers KR, Lyvers M (2005) Mood and impulsivity of recreational ecstasy users in the week following a “rave.” Addiction Research and Theory 13:43–52

    Article  Google Scholar 

  • Verkes RJ, Gijsman HJ, Pieters MSM, Schoemaker RC, de Visser S, Kuijpers M, Pennings EJM, de Bruin D, Van de Wijngaart G, Van Gerven JMA, Cohen AF (2001) Cognitive performance and serotonergic function in users of ecstasy. Psychopharmacology 153:196–202

    Article  PubMed  CAS  Google Scholar 

  • Weir E (2000) Raves: a review of the culture, the drugs and the prevention of harm. CMAJ 162:1843–1848

    PubMed  CAS  Google Scholar 

  • Yip JTH, Lee TMC (2005) Effect of ecstasy use on neuropsychological function: a study in Hong Kong. Psychopharmacology 179:620–628

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuropharmacology Research Group, School of Pharmacy, De Monfort University, The Gateway, Leicester, LE1 9BH, UK

    Kathryn S. Saadat & J. Martin Elliott

  2. School of Biomedical Sciences, Institute of Neuroscience, University of Nottingham, Nottingham, NG7 2RD, UK

    A. Richard Green

  3. School of Psychology, Institute of Neuroscience, University of Nottingham, Nottingham, NG7 2RD, UK

    Paula M. Moran

Authors
  1. Kathryn S. Saadat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Martin Elliott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Richard Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paula M. Moran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paula M. Moran.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saadat, K.S., Elliott, J.M., Green, A.R. et al. High-dose MDMA does not result in long-term changes in impulsivity in the rat. Psychopharmacology 188, 75–83 (2006). https://doi.org/10.1007/s00213-006-0470-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0470-8

Keywords

Search

Navigation