Cocaine kindling in mice - Responses to N-methyl-D,L-aspartate (NMDLA) and Ll-arginine

Yossef Itzhak

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Previous studies proposed the involvement of the N-methyl-D-aspartate (NMDA) type of glutamate receptors in the development of sensitization to the convulsive effect of cocaine (cocaine kindling). The present study was undertaken to determine, first, if cocaine kindling is associated with enhanced sensitivity of the NMDA receptor to the convulsive response of N-methyl-D,L-aspartate (NMDLA), and second, whether in vivo modulation of nitric oxide synthase (NOS) function regulates the development of cocaine kindling. The following results were observed: 1. Cocaine-kindled animals were significantly more susceptible to the convulsive effect of the NMDA receptor agonist NMDLA than saline controls; 2. Pretreatment with the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg; ip) blocked the development of cocaine kindling; 3. The protective effect of L-NAME was partially reversed with the coadministration of the NOS substrate, L-arginine (300 mg/kg; ip), but not D-arginine; and 4. L-Arginine (300 mg/kg; ip), but not D-arginine, amplified the development of cocaine kindling. Taken together, these findings suggest that supersensitivity of the NMDA receptor and activation of NOS may underlie the development of cocaine kindling.

Original languageEnglish
Pages (from-to)217-222
Number of pages6
JournalMolecular Neurobiology
Volume11
Issue number1-3
DOIs
StatePublished - Aug 1 1995

Fingerprint

N-Methylaspartate
Cocaine
Aspartic Acid
Arginine
N-Methyl-D-Aspartate Receptors
Nitric Oxide Synthase
NG-Nitroarginine Methyl Ester
Glutamate Receptors

Keywords

  • Cocaine
  • convulsions
  • nitric oxide (NO)
  • NMDA receptor
  • sensitization

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

Cocaine kindling in mice - Responses to N-methyl-D,L-aspartate (NMDLA) and Ll-arginine. / Itzhak, Yossef.

In: Molecular Neurobiology, Vol. 11, No. 1-3, 01.08.1995, p. 217-222.

Research output: Contribution to journalArticle

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