Rats exposed to acute pyrithiamine-induced thiamine deficiency are more sensitive to the amnestic effects of scopolamine and MK-801: examination of working memory, response selection, and reinforcement contingencies.

Abstract

Pyrithiamine-induced thiamine deficiency (PTD), which has been used as a model of Wernicke-Korsakoff syndrome (WKS), produces a range of neuropathological and behavioral abnormalities in rodents. The extent of the diencephalic damage produced by this treatment varies from moderate to extreme cell loss. The magnitude of working memory impairment tends to correlate with the degree of neuropathology. In this study a PTD protocol that produces moderate thalamic pathology was used to gain further insight into the neurobehavioral consequences of thiamine deficiency. Towards this end, two distinct manipulations were conducted. First, the differential outcomes procedure (DOP), which correlates specific reinforcers with specific to-be-remembered events, was applied to an operant version of matching-to-position (MTP). This behavioral manipulation was conducted to determine if the DOP would improve memory performance in PTD-treated rats, demonstrating some intact cognitive functions. Additionally, to assess the functional integrity of the cholinergic and glutamatergic systems, normal and PTD-treated rats were administered i.p. injections of scopolamine and MK-801. It was found that the DOP enhanced memory, but not acquisition performance, in both normal and PTD-treated rats. Furthermore, when administered scopolamine, but not MK-801, rats trained with the DOP continued to outperform rats trained with a non-differential outcomes procedure (NOP). However, PTD-treated rats, regardless of training procedure (DOP, NOP), were more disrupted by the 'amnestic' effects of both scopolamine and MK-801. The differential sensitivity of treatment groups to the amnestic effects of scopolamine and MK-801 reveals insights into the neurochemical correlates of memory processes and WKS.

• Authors: L M Savage, S R Pitkin, K M Knitowski
• Journal: Behavioural brain research (Behav Brain Res) Vol. 104 Issue 1-2 Pg. 13-26 (Oct 1999) ISSN: 0166-4328 [Print] Netherlands
• PMID: 11125732 (Publication Type: Journal Article)

Chemical References

• Pyrithiamine
• Dizocilpine Maleate
• Scopolamine

Topics

• Acute Disease
• Amnesia (chemically induced, metabolism)
• Analysis of Variance
• Animals
• Behavior, Animal (drug effects)
• Conditioning, Operant (drug effects)
• Disease Models, Animal
• Dizocilpine Maleate (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Korsakoff Syndrome (etiology, physiopathology)
• Male
• Memory, Short-Term (drug effects)
• Pyrithiamine
• Rats
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Scopolamine (pharmacology)
• Thalamus (drug effects, pathology)
• Thiamine Deficiency (chemically induced, metabolism, physiopathology)