Enhancement of opioid cataleptic response by cortical frontal deafferentation or intrastriatal injection of NMDA-receptor antagonists

Silvana Consolo, GianLuigi Forloni, Herbert Ladinsky, Elisabetta Palazzi

Research output: Contribution to journalArticle

Abstract

The cataleptic activity of morphine and methadone was markedly potentiated in frontally decorticated rats with no apparent changes in the onset or duration of action. Enhancement of the opioid cataleptic response was not due to changes in the availability of the drugs in the brain. The potentiation of methadone-induced catalepsy in decorticated rats was mimicked in naive rats by intrastriatal (i.s.) application of 2-amino-7-phosphonoheptanoic acid (AP7), a potent and selective antagonist of N-methyl-d-aspartate (NMDA) receptors. Therefore, degeneration of glutamatergic synapses following decortication could be responsible for the changes in behavioral effects caused by opioids. The failure of AP7 to elicit an effect after injection into the n. accumbens fits with the possibility of a selective involvement of the striatum in this phenomenon. That the striatum plays a critical role in the expression of opioid-induced catalepsy was substantiated by the findings that: (1) naloxone, an opiod antagonist, injected i.s., prevents the potentiation of catalepsy induced by methadone and morphine in decorticated animals, (2) oxotremorine, a muscarinic agonist, injected i.s., reverses the enhancement of opioid-catalepsy in decorticated rats. (3) earlier studies by others showed that ablation of the striatum had a facilitatory action on opioid-induced catalepsy. In conclusion, evidence is given that the corticostriatal pathway exerts an inhibitory effect upon narcotic-induced cataleptic behavior. The possibility that this effect is mediated through striatonigral GABAergic output is discussed. The data further suggest that the neuronal mechanisms through which the corticostriatal pathway mediates narcotic catalepsy is operative through activation of NMDA receptors within the striatum.

Original languageEnglish
Pages (from-to)97-103
Number of pages7
JournalBrain Research
Volume449
Issue number1-2
DOIs
Publication statusPublished - May 24 1988

Keywords

  • Corticostriatal pathway
  • Decortication
  • N-Methyl-d-aspartate receptor antagonist
  • Opioid catalepsy
  • Striatonigral GABAergic output
  • Striatum

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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