PMID- 16054778
OWN - NLM
STAT- MEDLINE
DCOM- 20060609
LR  - 20161124
IS  - 0376-8716 (Print)
IS  - 0376-8716 (Linking)
VI  - 81
IP  - 2
DP  - 2006 Feb 1
TI  - Chronic treatment with a serotonin(2) receptor (5-HT(2)R) agonist modulates the 
      behavioral and cellular response to (+)-3,4-methylenedioxymethamphetamine 
      [(+)-MDMA].
PG  - 117-27
AB  - 3,4-Methylenedioxymethamphetamine [MDMA; ecstasy] evokes a multifaceted 
      subjective experience in human users which includes stimulation, feelings of 
      well-being, mood elevation, empathy towards others as well as distortions in 
      time, sensation and perception. Aspects of this unique psychopharmacology of MDMA 
      are thought to be related to its potent actions to release serotonin (5-HT) and 
      indirectly stimulate the 5-HT(2A) receptor (5-HT(2A)R). In the present studies, 
      we examined the interrelationship between down-regulation of 5-HT(2A)R expression 
      and the behaviorally stimulatory effects generated by acute administration of 
      (+)-MDMA, the most potent enantiomer of (+/-)-MDMA. Male Sprague-Dawley rats were 
      chronically treated with the preferential 5-HT(2A)R agonist 
      2,5-dimethoxy-4-iodoamphetamine (DOI) which has been shown to down-regulate 
      expression of the 5-HT(2A)R, but not the closely related 5-HT(2C)R. While chronic 
      DOI treatment did not alter the functional sensitivity of either the 5-HT(2A)R or 
      5-HT(2C)R, this regimen enhanced (+)-MDMA-evoked hyperactivity. Subsequent 
      analysis of c-Fos and 5-HT(2A)R immunoreactivity in brain sections demonstrated 
      that DOI treatment decreased the number of (+)-MDMA-induced c-Fos immunopositive 
      nuclei and 5-HT(2A)R immunostaining in select cortical and striatal areas. These 
      results indicate that chronic DOI exposure results in an enhanced behavioral 
      response to (+)-MDMA and in a pattern of neuronal activation which resembles that 
      seen in psychostimulant sensitization. These data also suggest that expression of 
      the 5-HT(2A)R in the NAc and PFC may play a role in the sensitivity to the 
      locomotor-stimulating effects of (+)-MDMA and in the processes of neural 
      regulation upon repeated psychostimulant administration.
FAU - Ross, Julie D
AU  - Ross JD
AD  - Center for Addiction Research, Department of Pharmacology and Toxicology, 
      University of Texas Medical Branch, 301 University Blvd., Galveston TX 
      77555-1031, USA.
FAU - Herin, David V
AU  - Herin DV
FAU - Frankel, Paul S
AU  - Frankel PS
FAU - Thomas, Mary L
AU  - Thomas ML
FAU - Cunningham, Kathryn A
AU  - Cunningham KA
LA  - eng
GR  - F31 DA015272-03/DA/NIDA NIH HHS/United States
GR  - DA 13595/DA/NIDA NIH HHS/United States
GR  - DA15272/DA/NIDA NIH HHS/United States
GR  - F31 DA015272/DA/NIDA NIH HHS/United States
GR  - F31 DA015272-01/DA/NIDA NIH HHS/United States
GR  - DA 16500/DA/NIDA NIH HHS/United States
GR  - DA 06057/DA/NIDA NIH HHS/United States
GR  - F31 DA015272-02/DA/NIDA NIH HHS/United States
GR  - DA 00260/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20050728
PL  - Ireland
TA  - Drug Alcohol Depend
JT  - Drug and alcohol dependence
JID - 7513587
RN  - 0 (Amphetamines)
RN  - 0 (Hallucinogens)
RN  - 0 (Pyrazines)
RN  - 0 (Receptors, Serotonin, 5-HT2)
RN  - 0 (Serotonin 5-HT2 Receptor Agonists)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 62C3N7238U (6-chloro-2-(1-piperazinyl)pyrazine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - OOM10GW9UE (4-iodo-2,5-dimethoxyphenylisopropylamine)
SB  - IM
MH  - Amphetamines/*therapeutic use
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Down-Regulation
MH  - Hallucinogens/*adverse effects
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*adverse effects
MH  - Pyrazines/administration & dosage
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin, 5-HT2/*therapeutic use
MH  - *Serotonin 5-HT2 Receptor Agonists
MH  - Serotonin Agents/*adverse effects
MH  - Serotonin Receptor Agonists/administration & dosage
EDAT- 2005/08/02 09:00
MHDA- 2006/06/10 09:00
CRDT- 2005/08/02 09:00
PHST- 2005/01/21 00:00 [received]
PHST- 2005/06/09 00:00 [revised]
PHST- 2005/06/13 00:00 [accepted]
PHST- 2005/08/02 09:00 [pubmed]
PHST- 2006/06/10 09:00 [medline]
PHST- 2005/08/02 09:00 [entrez]
AID - S0376-8716(05)00194-8 [pii]
AID - 10.1016/j.drugalcdep.2005.06.004 [doi]
PST - ppublish
SO  - Drug Alcohol Depend. 2006 Feb 1;81(2):117-27. doi: 
      10.1016/j.drugalcdep.2005.06.004. Epub 2005 Jul 28.