PMID- 15193525 OWN - NLM STAT- MEDLINE DCOM- 20040825 LR - 20131121 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 1013 IP - 2 DP - 2004 Jul 9 TI - Protein kinase C inhibition differentially affects 3,4-methylenedioxymethamphetamine-induced dopamine release in the striatum and prefrontal cortex of the rat. PG - 168-73 AB - The acute administration of 3,4-methylenedioxymethamphetamine (MDMA) elevates extracellular concentrations of dopamine (DA) and serotonin (5-HT) in the rat striatum and medial prefrontal cortex (mPFC). The release of DA induced by MDMA is thought to involve both transporter and impulse-mediated processes. Furthermore, the impulse-dependent release of DA in the striatum elicited by MDMA appears to involve 5-HT2 receptor activation. Since 5-HT2 receptors are known to utilize protein kinase C (PKC) for intracellular signaling, we examined the effects of modulators of PKC activity on DA release stimulated by MDMA. Reverse dialysis of the PKC inhibitors bisindolylmaleimide I (BIM; 30 microM) or chelerythrine chloride (100 microM) through a microdialysis probe significantly attenuated the MDMA (10 mg/kg, i.p.)-induced increase in the extracellular concentration of DA in the striatum. In contrast, BIM did not significantly alter the increase in the extracellular concentration of DA in the striatum elicited by amphetamine (5 mg/kg, i.p.). Reverse dialysis of a PKC activator, phorbol 12,13-dibutyrate (PDBu) (0.5 microM), through the microdialysis probe into the striatum, significantly increased MDMA-induced DA release. In contrast to the inhibitory effects of the PKC inhibitors on MDMA-induced DA release in the striatum, intracortical infusion of BIM enhanced MDMA-induced release of DA in the mPFC. These data suggest that PKC-mediated signaling pathways differentially modulate MDMA-induced DA release from mesocorticolimbic and nigrostriatal neurons. FAU - Nair, Sunila G AU - Nair SG AD - College of Pharmacy, University of Cincinnati, 3223 Eden Avenue, Cincinnati, OH 45267, USA. FAU - Gudelsky, Gary A AU - Gudelsky GA LA - eng GR - DA 07427/DA/NIDA NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Serotonin Agents) RN - EC 2.7.11.13 (Protein Kinase C) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Corpus Striatum/drug effects/*metabolism MH - Dopamine/*metabolism MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Prefrontal Cortex/drug effects/*metabolism MH - Protein Kinase C/*antagonists & inhibitors MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin Agents/*pharmacology MH - Signal Transduction/physiology EDAT- 2004/06/15 05:00 MHDA- 2004/08/26 05:00 CRDT- 2004/06/15 05:00 PHST- 2004/04/01 00:00 [accepted] PHST- 2004/06/15 05:00 [pubmed] PHST- 2004/08/26 05:00 [medline] PHST- 2004/06/15 05:00 [entrez] AID - S0006899304005499 [pii] AID - 10.1016/j.brainres.2004.04.007 [doi] PST - ppublish SO - Brain Res. 2004 Jul 9;1013(2):168-73. doi: 10.1016/j.brainres.2004.04.007.