Effects of sigma ligands on mouse cerebellar cyclic guanosine monophosphate (cGMP) levels in vivo: further evidence for a functional modulation of N-methyl-d-aspartate (NMDA) receptor complex-mediated events by sigma ligands

Tadimeti S. Rao, Steve J. Mick, Julie A. Cler, Mark R. Emmett, Vickie M. Dilworth, Patricia C. Contreras, Nancy M. Gray, Paul L. Wood, Smriti Iyengar

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34 Scopus citations

Abstract

In the present investigation, the effects of sigma ligands [WY-47384 {;8-fluoro-2,3,4,5-tetrahydro-2[3-(3-pyridinyl)propyl)1H- pyrido(4, 3b)indole}, (+)-pentazocine, (+)-SFK 10,047 (N-allylnormetazocine), mafoprazine, opipramol, dextromethorphan, dextrorphan, (+)-3-PPP [3-(3-hydroxyphenyl)-N-propylpiperidine], (-)-butaclamol, DTG [1,3-di(2-tolyl)guanidine], rimcazole, ifenprodil and BMY-14802 {α-(fluorophenyl)-4-(5-fluoropyrimidinyl)-1-piperazine butanol}] on harmaline-, pentylenetetrazol (PTZ)-, methamphetamine (MA)- and d-serine-induced increases in mouse cerebellar levels of cGMP were determined. Ifenprodil, BMY-14802, dextromethorphan, dextrorphan, (+)-SKF 10,047, opipramol and mafoprazine reversed harmaline-, PTZ-, MA- and d-serine-induced increases in levels of cGMP. Rimcazole reversed only the harmaline-induced response. WY-47384 reversed harmaline-, MA-, d-serine-, but not PTZ- or quisqualate-induced increases in levels of cGMP. (+)-Pentazocine attenuated harmaline- and d-serine-, but not PTZ- and MA-induced cGMP responses. Haloperidol did not affect harmaline- and d-serine-induced cGMP responses. (+)-3-PPP and (-)-butaclamol did not affect any of the responses studied. Furthermore, (+)-3-PPP-induced increases in levels of cGMP were reversed by the competitive N-methyl-d-aspartate (NMDA) antagonist, CPP} 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the non-competitive NMDA antagonist, (+)-MK-801 (dizocilipine maleate), the NMDA-associated glycine receptor antagonist, HA-966 (3-amino-1-hydroxypyrrolidin-2-one), the partial glycine agonist, DCS (d-cycloserine) as well as by the sigma ligands, ifenprodil, WY-47384, (+)-pentazocine, (+)-SKF 10,047, dextromethorphan and dextrorphan but not by rimcazole. These data further support functional modulation by sigma ligands of events mediated by the NMDA receptor complex established in earlier investigations.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalBrain Research
Volume561
Issue number1
DOIs
StatePublished - Oct 4 1991
Externally publishedYes

Keywords

  • Cyclic guanosine monophosphate
  • Harmaline, Pentylenetetrazol
  • Methamphetamine, Sigma receptor
  • N-Methyl-d-aspartate

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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