Repeated exposure to MDMA and amphetamine: sensitization, cross-sensitization, and response to dopamine D1- and D2-like agonists
- 413 Downloads
Acute exposure to (±) 3, 4-methylenedioxymethamphetamine (MDMA) produces hyperlocomotion that is preferentially expressed in the periphery of closed chambers. Following repeated administration, however, a sensitized hyperlocomotor response is preferentially expressed in the center of an activity box, so that the response resembles the more generalized activity that is produced by d-amphetamine (AMPH).
The present study was designed to determine whether common neuroadaptations underlie the acute and sensitized responses to MDMA and AMPH.
Rats were pretreated with five daily injections of MDMA (10.0 mg/kg), AMPH (2.0 mg/kg), or saline. Following a 2-day drug-free period, dose–response curves for hyperactivity produced by MDMA (2.5–10.0 mg/kg), AMPH (0.5–2.0 mg/kg), SKF-81297 (1.0–2.0 mg/kg), or quinpirole (0.25–1.0 mg/kg) were obtained.
Effects of MDMA and AMPH were increased by pretreatment with both drugs. The sensitized response following MDMA exposure was preferentially expressed in the center compartment, but, following AMPH pretreatment, the sensitized response was observed in both compartments. Cross-sensitization was unidirectional; AMPH pretreatment failed to sensitize to the effects of MDMA, but MDMA pretreatment sensitized to the effects of AMPH. MDMA and AMPH pretreatment produced marginal increases in the effects of SKF-81297. The response to quinpirole was, however, greater following MDMA, but not AMPH, pretreatment.
These data suggest that repeated MDMA exposure produces sensitization via a unique neurochemical effect.
KeywordsMDMA Amphetamine Sensitization SKF-81297 Quinpirole Dopamine Hyperactivity
Royal Society of New Zealand Marsden Fund
Conflict of interest
The authors do not declare any conflict of interest.
- Crombag HS, Badiani A, Chan J, Dell’Orco J, Dineen SP, Robinson TE (2001) The ability of environmental context to facilitate psychomotor sensitization to amphetamine can be dissociated from its effect on acute drug responsiveness and on conditioned responding. Neuropsychopharmaclogy 24:680–690CrossRefGoogle Scholar
- Depoortere R, Boulay D, Perrault G, Bergis O, Decobert M, Francon D, Jung M, Simiand J, Soubrie P, Scatton B (2003) SSR 181507, a dopamine D2 receptor antagonist and 5-HT1A receptor agonist. II: behavioural profile predictive of an atypical antipsychotic activity. Neuropsychopharmacology 28:1889–1902PubMedCrossRefGoogle Scholar
- Lévesque D, Diaz J, Pilon C, Martres MP, Giros B, Souil E, Schott D, Morgat JL, Schwartz JC, Sokoloff P (1992) Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3 H]hydroxy-N, N-di-n-propyl-2-aminotetralin. Proc Natl Acad Sci U S A 89:8155–8159PubMedCrossRefGoogle Scholar
- Modi GM, Yang PB, Swann AC, Dafny N (2006) Chronic exposure to MDMA (ecstasy) elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants. Behav Brain Funct 4. doi: 10.1186/1744-9081-2-1
- Ramos M, Goni-Allo B, Aguirre N (2005a) Administration of SCH-23390 into the medial prefrontal cortex blocks the expression of MDMA-induced behavioral sensitization in rats: an effect mediated by 5-HT2C receptor stimulation and not by D1 receptor blockade. Neuropsychopharmacology 30:2180–2191PubMedCrossRefGoogle Scholar
- Richtand NM, Welge JA, Levant B, Logue AD, Hayes S, Pritchard LM, Geracioti TD, Coolen LM, Berger SP (2003) Altered behavioral response to dopamine D3 receptor agonists 7-OH-DPAT and PD 128907 following repetitive amphetamine administration. Neuropsychopharmacology 28:1422–1432PubMedCrossRefGoogle Scholar
- Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347(6289):146–151Google Scholar
- Stanwood GD, Artymyshyn RP, Kung MP, Kung HF, Lucki I, McGonigle P (2000) Quantitative autoradiographic mapping of rat brain dopamine D3 binding with [(125)I]7-OH-PIPAT: evidence for the presence of D3 receptors on dopaminergic and nondopaminergic cell bodies and terminals. J Pharmacol Exp Ther 295:1223–1231PubMedGoogle Scholar