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NMDA antagonists make learning and recall state-dependent.

A. Jackson1, W. Koek, F.C. Colpaert

  • 1Neurobiology Division, Fondax, Puteaux, France Present address: Merck, Sharp and Dohme Neuroscience Research Labs, Terlings Park, Eastwick Rd, Harlow, Essex CM20 2QR, UK.

Behavioural Pharmacology
|August 1, 1992
PubMed
Summary

NMDA antagonists like ketamine create a drug-dependent state, not memory deficits. Rats require the same drug state for recall of learned tasks, demonstrating state-dependent learning.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • NMDA receptor antagonists are widely studied for their effects on cognition.
  • Previous research often attributed cognitive impairments to NMDA antagonists, suggesting memory deficits.

Purpose of the Study:

  • To investigate the effects of NMDA receptor antagonists on learned response retention.
  • To determine if NMDA antagonists induce state-dependent learning rather than memory impairment.

Main Methods:

  • Rats were trained on a lever-pressing task with food reward.
  • State-dependency was assessed by testing response retention under different drug conditions (drug vs. saline).
  • NMDA antagonists tested included ketamine, phencyclidine, MK-801, and CGS 19755.

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Main Results:

  • State-dependency was observed with all tested NMDA antagonists.
  • Response transfer failed when testing conditions differed from training conditions (drug-to-saline or saline-to-drug).
  • Doses causing state-dependency were lower than those impairing acquisition.

Conclusions:

  • NMDA antagonists induce state-dependent learning, where recall is contingent on the training drug state.
  • The findings challenge the notion that NMDA antagonists cause general memory or retention deficits.
  • Disorganization of behavior by NMDA antagonists may stem from this induced state-dependency.