PMID- 15841107
OWN - NLM
STAT- MEDLINE
DCOM- 20060124
LR  - 20151119
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 30
IP  - 12
DP  - 2005 Dec
TI  - 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.
PG  - 2180-91
AB  - Akin to what has been reported for cocaine, systemic administration of the 
      dopamine D1 receptor antagonist, SCH 23390 
      ((R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine 
      hydrochloride), blocks the expression but not the induction of 
      3,4-methylenedioxymethamphetamine (MDMA)-induced behavioral sensitization. Since 
      the medial prefrontal cortex (mPFC) appears to regulate the expression of 
      sensitization to cocaine, this study examined whether microinjection of SCH 23390 
      into the mPFC would alter the expression of MDMA sensitization. Saline or MDMA 
      was administered for 5 consecutive days. After 12 days of withdrawal, rats 
      received a bilateral intra-mPFC microinjection of SCH 23390 or saline followed by 
      an intraperitoneal (i.p.) challenge dose of MDMA. While SCH 23390 enhanced 
      locomotion in MDMA-naive rats, it completely suppressed the expression of 
      sensitization in MDMA-pretreated animals. Since, SCH 23390 has a fairly good 
      affinity for 5-HT(2C) receptors, we went further to study the role of mPFC D1 and 
      5-HT(2C) receptors in this, apparently, paradoxical effect shown by SCH 23390. 
      Thus, the microinjection of both SKF 81297 
      (R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine 
      hydrobromide) and MK 212 (6-chloro-2-(1-piperazinyl)pyrazine hydrochloride), a D1 
      and 5-HT(2C) receptor agonist, respectively, blocked MDMA sensitization. By 
      contrast, the 5-HT(2C) receptor antagonist, RS 102221 
      (8-[5-(2,4-dimethoxy-5-(4-trifluoromethylphenylsulfonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4,5]decane-2,4-dione 
      hydrochloride), had no effect in MDMA-naive or MDMA-sensitized animals, but 
      reversed the effects of SCH 23390 in MDMA-pretreated rats. These results 
      demonstrate that suppression of MDMA-induced sensitization by SCH 23390 is 
      mediated by 5-HT(2C) receptor stimulation in the mPFC and not by the blockade of 
      mPFC D1 receptors. Furthermore, these data indicate that stimulation of 5-HT(2C) 
      receptors by SCH 23390 is not a minor issue and should be considered when 
      interpreting future data.
FAU - Ramos, Maria
AU  - Ramos M
AD  - Departamento de Farmacologia, Facultad de Medicina, Universidad de Navarra, 
      C/Irunlarrea 1, Pamplona 31008, Spain.
FAU - Goni-Allo, Beatriz
AU  - Goni-Allo B
FAU - Aguirre, Norberto
AU  - Aguirre N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 
      (8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione)
RN  - 0 (Benzazepines)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Hallucinogens)
RN  - 0 (Pyrazines)
RN  - 0 (Receptor, Serotonin, 5-HT2C)
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (Spiro Compounds)
RN  - 0 (Sulfonamides)
RN  - 62C3N7238U (6-chloro-2-(1-piperazinyl)pyrazine)
RN  - 71636-61-8 (SK&F 81297)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Benzazepines/administration & dosage/*pharmacology
MH  - Dopamine Antagonists/administration & dosage/*pharmacology
MH  - Hallucinogens/*pharmacology
MH  - Male
MH  - Microinjections
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Prefrontal Cortex/*physiology
MH  - Pyrazines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Serotonin, 5-HT2C/*drug effects
MH  - Receptors, Dopamine D1/*drug effects
MH  - Serotonin Receptor Agonists/pharmacology
MH  - Spiro Compounds/pharmacology
MH  - Sulfonamides/pharmacology
EDAT- 2005/04/21 09:00
MHDA- 2006/01/25 09:00
CRDT- 2005/04/21 09:00
PHST- 2005/04/21 09:00 [pubmed]
PHST- 2006/01/25 09:00 [medline]
PHST- 2005/04/21 09:00 [entrez]
AID - 1300735 [pii]
AID - 10.1038/sj.npp.1300735 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2005 Dec;30(12):2180-91. doi: 10.1038/sj.npp.1300735.