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
Autor: | Norberto Aguirre, Beatriz Goñi-Allo, María Jiménez Ramos |
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Rok vydání: | 2005 |
Předmět: |
Male
Agonist Microinjections medicine.drug_class N-Methyl-3 4-methylenedioxyamphetamine Prefrontal Cortex Stimulation RS-102221 Motor Activity Pharmacology chemistry.chemical_compound Dopamine receptor D1 mental disorders Receptor Serotonin 5-HT2C medicine Animals Spiro Compounds heterocyclic compounds Rats Wistar Sensitization Sulfonamides SCH-23390 Behavior Animal Receptors Dopamine D1 Benzazepines Receptor antagonist Rats Serotonin Receptor Agonists 5-HT2C receptor Psychiatry and Mental health medicine.anatomical_structure nervous system chemistry Pyrazines Hallucinogens Dopamine Antagonists psychological phenomena and processes |
Zdroj: | Neuropsychopharmacology. 30:2180-2191 |
ISSN: | 1740-634X 0893-133X |
DOI: | 10.1038/sj.npp.1300735 |
Popis: | 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. |
Databáze: | OpenAIRE |
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