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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. 2005 Dec; 30(12):2180-91.N

Abstract

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-naïve 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-naïve 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.

Authors+Show Affiliations

Departamento de Farmacología, Facultad de Medicina, Universidad de Navarra, C/Irunlarrea 1, Pamplona 31008, Spain.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15841107

Citation

Ramos, María, et al. "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 : Official Publication of the American College of Neuropsychopharmacology, vol. 30, no. 12, 2005, pp. 2180-91.
Ramos M, Goñi-Allo B, Aguirre N. 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. 2005;30(12):2180-91.
Ramos, M., Goñi-Allo, B., & Aguirre, N. (2005). 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 : Official Publication of the American College of Neuropsychopharmacology, 30(12), 2180-91.
Ramos M, Goñi-Allo B, Aguirre N. 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. 2005;30(12):2180-91. PubMed PMID: 15841107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ramos,María, AU - Goñi-Allo,Beatriz, AU - Aguirre,Norberto, PY - 2005/4/21/pubmed PY - 2006/1/25/medline PY - 2005/4/21/entrez SP - 2180 EP - 91 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 30 IS - 12 N2 - 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-naïve 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-naïve 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. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/15841107/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_ L2 - http://dx.doi.org/10.1038/sj.npp.1300735 DB - PRIME DP - Unbound Medicine ER -