A performance-dependent adjustment of the retention interval in a delayed non-matching-to-position paradigm differentiates effects of amnestic drugs in rats

Eur J Pharmacol. 2000 Sep 1;403(1-2):87-93. doi: 10.1016/s0014-2999(00)00480-5.

Abstract

Operant delayed non-matching-to-position (delayed non-matching-to-position) tasks have been widely used as tests of working memory in rats, but have suffered some loss in sensitivity to differentiating selective mnemonic from non-mnemonic deficits due to floor and ceiling effects. To circumvent this problem, a novel delayed non-matching-to-position was developed in which the retention interval was adjusted on a trial-by-trial basis to hold performance accuracy at an intermediate value. The present study assessed the effects of three amnestic drugs in this delayed non-matching-to-position. Rats were administered (i.p.) NMDA receptor antagonist ((5R,10S)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo[a,d,] cyclohepten-5,10-imine (Dizocilpine or MK-801), muscarinic receptor antagonist (-)-scopolamine hydrobromide (scopolamine), or cannabinoid receptor agonist ((R)-(+)-[2, 3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1, 4-benzoxazin-6-yl]-1-naphthalenylmethanone) (WIN 55, 212-2). At high doses, both MK-801 (0.12-0.25 mg/kg) and scopolamine (0.25 mg/kg) produced deficits not selective to working memory. At low doses, scopolamine (0.06-0.12 mg/kg) and MK-801 (0.06 mg/kg) produced no deficits in any mnemonic or secondary measures. WIN 55, 212-2 produced deficits at 2.0 mg/kg that were consistent with a specific impairment of working memory. Using this particular delayed non-matching-to-position revealed that consistent changes in performance accuracy at the short retention interval were evident for scopolamine and MK-801, at times in the absence of changes in response tendency, which are consistent with an interpretation that these drugs produce general deficits in reference or procedural memory. In contrast, cannabinoid-induced deficits in choice accuracy support previous reports of delay-dependent deficits. Together, these data suggest that this delayed non-matching-to-position task is able to differentiate deficit patterns of amnestic drugs, and isolate the effects of motivational side effects of drugs from working memory measurement.

Publication types

  • Comparative Study

MeSH terms

  • Amnesia / chemically induced*
  • Animals
  • Behavior, Animal / drug effects
  • Benzoxazines
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Male
  • Memory / drug effects*
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Psychomotor Performance / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Retention, Psychology / drug effects*
  • Scopolamine / pharmacology

Substances

  • Benzoxazines
  • Morpholines
  • Naphthalenes
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Dizocilpine Maleate
  • Scopolamine