Skip to main content
×
Home
    • Aa
    • Aa
  • The International Journal of Neuropsychopharmacology, Volume 15, Issue 6
  • July 2012, pp. 811-824

Distinct periods of developmental sensitivity to the effects of 3,4-(±)-methylenedioxymethamphetamine (MDMA) on behaviour and monoamines in rats

Abstract
Abstract

Previous findings showed allocentric and egocentric learning deficits in rats after MDMA treatment from postnatal days (PD) 11–20 but not after treatment from PD 1–10. Shorter treatment periods (PD 1–5, 6–10, 11–15, or 16–20) resulted in allocentric learning deficits averaged across intervals but not for any interval individually and no egocentric learning deficits individually or collectively. Whether this difference was attributable to treatment length or age at the start of treatment was unclear. In the present experiment rat litters were treated on PD 1–10, 6–15, or 11–20 with 0, 10, or 15 mg/kg MDMA q.i.d. at 2-h intervals. Two male/female pairs/litter received each treatment. One pair/litter received acoustic startle with prepulse inhibition, straight channel swimming, Cincinnati water maze (CWM), and conditioned fear in a latent inhibition paradigm. The other pair/litter received locomotor activity, straight channel swimming, Morris water maze (MWM), and locomotor activity retest with MK-801 challenge. MDMA impaired CWM learning following PD 6–15 or 11–20 exposure. In MWM acquisition, all MDMA-treated groups showed impairment. During reversal and shift, the PD 6–15 and PD 11–20 MDMA-treated groups were significantly impaired. Reductions in locomotor activity were most evident after PD 6–15 treatment while increases in acoustic startle were most evident after PD 1–10 treatment. After MK-801 challenge, MDMA-treated offspring showed less locomotion compared to controls. Region-specific changes in brain monoamines were also observed but were not significantly correlated with behavioural changes. The results show that PD 11–20 exposure to MDMA caused the largest long-term cognitive deficits followed by PD 6–15 exposure with PD 1–10 exposure least affected. Other effects, such as those upon MK-801-stimulated locomotion showed greatest effects after PD 1–10 MDMA exposure. Hence, each effect has a different window of developmental susceptibility.

Copyright
Corresponding author
*Address for correspondence: C. V. Vorhees, Ph.D., Division of Neurology, Cincinnati Children's Research Foundation, 3333 Burnet Ave, ML 7044, Cincinnati, OH 45229, USA. Tel.: (513) 636-8622Fax: (513) 636-3912Email: charles.vorhees@cchmc.org [C.V.V.]
Email: michael.williams@cchmc.org [M.T.W.]
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

ME Bronson , W Jiang , CR Clark , J DeRuiter (1994). Effects of designer drugs on the chicken embryo and 1-day-old chicken. Brain Research Bulletin 34, 143150.

DP Cain (1997). Prior non-spatial pretraining eliminates sensorimotor disturbances and impairments in water maze learning caused by diazepam. Psychopharmacology (Berlin) 130, 313319.

B Clancy , BL Finlay , RB Darlington , KJ Anand (2007 a). Extrapolating brain development from experimental species to humans. Neurotoxicology 28, 931937.

B Clancy , B Kersh , J Hyde , RB Darlington , . (2007 b). Web-based method for translating neurodevelopment from laboratory species to humans. Neuroinformatics 5, 7994.

MA Cohen , MR Skelton , TL Schaefer , GA Gudelsky , . (2005). Learning and memory after neonatal exposure to 3,4-methylenedioxymethamphetamine (ecstasy) in rats: Interaction with exposure in adulthood. Synapse 57, 148159.

CE Grace , TL Schaefer , DL Graham , MR Skelton , . (2010). Effects of inhibiting neonatal methamphetamine-induced corticosterone release in rats by adrenal autotransplantation on later learning, memory, and plasma corticosterone levels. International Journal of Developmental Neuroscience 28, 331342.

NR Herring , TL Schaefer , GA Gudelsky , CV Vorhees , . (2008). Effect of (+)-methamphetamine on path integration learning, novel object recognition, and neurotoxicity in rats. Psychopharmacology (Berlin) 199, 637650.

E Ho , L Karimi-Tabesh , G Koren (2001). Characteristics of pregnant women who use ecstasy (3, 4-methylenedioxymethamphetamine). Neurotoxicology and Teratology 23, 561567.

DG Moore , JD Turner , AC Parrott , JE Goodwin , . (2010). During pregnancy, recreational drug-using women stop taking ecstasy (3,4-methylenedioxy-N-methylamphetamine) and reduce alcohol consumption, but continue to smoke tobacco and cannabis: initial findings from the Development and Infancy Study. Journal of Psychopharmacology 24, 14031410.

RG Morris , E Anderson , GS Lynch , M Baudry (1986). Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319, 774776.

D Rice , S Barone (2000). Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environmental Health Perspectives 108 (Suppl. 3), 511533.

D Saucier , EL Hargreaves , F Boon , CH Vanderwolf , . (1996). Detailed behavioral analysis of water maze acquisition under systemic NMDA or muscarinic antagonism: nonspatial pretraining eliminates spatial learning deficits. Behavioral Neuroscience 110, 103116.

MR Skelton , TL Schaefer , NR Herring , CE Grace , . (2009). Comparison of the developmental effects of 5-methoxy-N,N-diisopropyltryptamine (Foxy) to (±)-3,4-methylenedioxymethamphetamine (ecstasy) in rats. Psychopharmacology (Berlin) 204, 287297.

MR Skelton , MT Williams , CV Vorhees (2006). Treatment with MDMA from P11–20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats. Psychopharmacology (Berlin) 189, 307318.

MR Skelton , MT Williams , CV Vorhees (2008). Developmental effects of 3,4-methylenedioxymethamphetamine: a review. Behavioral Pharmacology 19, 91–111.

MS Sodhi , E Sanders-Bush (2004). Serotonin and brain development. International Reviews of Neurobiology 59, 111174.

CV Vorhees (1987). Maze learning in rats: a comparison of performance in two water mazes in progeny prenatally exposed to different doses of phenytoin. Neurotoxicology and Teratology 9, 235241.

CV Vorhees , TM Reed , MR Skelton , MT Williams (2004). Exposure to 3,4-methylenedioxymethamphetamine (MDMA) on postnatal days 11–20 induces reference but not working memory deficits in the Morris water maze in rats: implications of prior learning. International Journal of Developmental Neuroscience 22, 247259.

CV Vorhees , TL Schaefer , MR Skelton , CE Grace , . (2009). (±)3,4-Methylenedioxymethamphetamine (MDMA) dose-dependently impairs spatial learning in the morris water maze after exposure of rats to different five-day intervals from birth to postnatal day twenty. Developmental Neuroscience 31, 107120.

CV Vorhees , TL Schaefer , MT Williams (2007). Developmental effects of±-methylenedioxymethamphetamine on spatial vs. path integration learning: effects of dose distribution. Synapse 61, 488499.

CV Vorhees , MT Williams (2006). Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature Protocols 1, 848858.

MT Williams , LL Morford , SL Wood , SL Rock , . (2003). Developmental 3,4-methylenedioxymethamphetamine (MDMA) impairs sequential and spatial but not cued learning independent of growth, litter effects or injection stress. Brain Research 968, 89–101.

MT Williams , CV Vorhees , F Boon , AJ Saber , . (2002). Methamphetamine exposure from postnatal day 11 to 20 causes impairments in both behavioral strategies and spatial learning in adult rats. Brain Research 958, 312321.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords: