PMID- 16434566
OWN - NLM
STAT- MEDLINE
DCOM- 20060609
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 317
IP  - 2
DP  - 2006 May
TI  - Repeated adolescent 3,4-methylenedioxymethamphetamine (MDMA) exposure in rats 
      attenuates the effects of a subsequent challenge with MDMA or a 
      5-hydroxytryptamine(1A) receptor agonist.
PG  - 838-49
AB  - Adolescent users of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) may 
      escalate their dose because of the development of tolerance. We examined the 
      influence of intermittent adolescent MDMA exposure on the behavioral, 
      physiological, and neurochemical responses to a subsequent MDMA "binge" or to a 
      5-hydroxytryptamine(1A) (5-HT(1A)) receptor challenge. Male Sprague-Dawley rats 
      were given MDMA (10 mg/kg b.i.d.) or saline every 5th day on postnatal days (PDs) 
      35 to 60. One week later on PD 67, animals were challenged with either multiple 
      doses of MDMA (four 5 or 10 mg/kg doses) or a single dose of the 5-HT(1A) agonist 
      8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.1 or 0.5 mg/kg). Adolescent 
      MDMA exposure partially attenuated the hyperthermic effects of the PD 67 MDMA 
      challenge, completely blocked the locomotor hypoactivity otherwise observed on 
      the day after the challenge, and also prevented MDMA-induced serotonin 
      neurotoxicity assessed on PD 74 by measuring regional [(3)H]citalopram binding to 
      the serotonin transporter (SERT). Adolescent MDMA-treated animals also showed a 
      partial attenuation of the serotonin syndrome but not the hypothermic response to 
      the high dose of 8-OH-DPAT. However, there was no effect of MDMA administration 
      on regional 
      [(3)H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide 
      trihydrochloride (WAY-100635) binding to 5-HT(1A) receptors in the brain or 
      spinal cord. These results suggest that chronic, intermittent MDMA exposure 
      during adolescence induces neuroadaptive changes that can protect against the 
      adverse consequences of a subsequent dose escalation. On the other hand, the same 
      exposure pattern appears to produce a partial 5-HT(1A) receptor desensitization, 
      which may negatively influence the therapeutic responses of chronic MDMA users 
      treated with serotonergic agents for various affective or anxiety disorders.
FAU - Piper, Brian J
AU  - Piper BJ
AD  - Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 
      01003-7710, USA.
FAU - Vu, Huyen L
AU  - Vu HL
FAU - Safain, Mina G
AU  - Safain MG
FAU - Oliver, Andrew J
AU  - Oliver AJ
FAU - Meyer, Jerrold S
AU  - Meyer JS
LA  - eng
PT  - Journal Article
DEP - 20060124
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 0 (Serotonin 5-HT1 Receptor Agonists)
RN  - 71IH826FEG 
      (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide)
RN  - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology
MH  - Aging/metabolism
MH  - Animals
MH  - Behavior, Animal/*drug effects/physiology
MH  - Body Weight/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - *Neurotoxicity Syndromes/metabolism/physiopathology/prevention & control
MH  - Piperazines/pharmacology
MH  - Pyridines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Serotonin 5-HT1 Receptor Agonists
EDAT- 2006/01/26 09:00
MHDA- 2006/06/10 09:00
CRDT- 2006/01/26 09:00
PHST- 2006/01/26 09:00 [pubmed]
PHST- 2006/06/10 09:00 [medline]
PHST- 2006/01/26 09:00 [entrez]
AID - jpet.105.095760 [pii]
AID - 10.1124/jpet.105.095760 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2006 May;317(2):838-49. doi: 10.1124/jpet.105.095760. Epub 
      2006 Jan 24.