Learning ability is a key outcome determinant of GSK-3 inhibition on visuospatial memory in rats.
Learning aptitude has never been a focus of visuospatial performance studies, particularly on memory consolidation and reconsolidation. The aim of this study was to determine the consequences of learning ability on memory consolidation/reconsolidation following inhibition of glucose synthase kinase-3 (GSK-3) by 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8). The anxiety-like nature of rats was characterized in the elevated plus maze. The rats were then trained for four days in the Morris water maze (MWM) and classified as 'superior', 'intermediate' or 'inferior' learners. There were no major differences between superior, intermediate or inferior learners with respect to anxiety which might have influenced learning. After training (day-5), TDZD-8 (2.0 mg/kg) was administered and half of the cohort were exposed to a MWM retrieval trial. Ten days later, animals were subjected to repeated MWM learning. TDZD-8 without a retrieval trial impaired subsequent reconsolidation in inferior learners, but enhanced it in superior learners. There was no modification of performance in intermediate learners. In TDZD-8-treated subjects exposed to retrieval, the pattern of outcomes was identical whereby impairment of reconsolidation occurred in inferior learners, enhancement occurred in superior learners but there was no modification of performance in intermediate learners. Thus, learning ability was a key determinant of the qualitative outcome from GSK-3 inhibition on visuospatial memory.
Federal State Budgetary Scientific Institution, P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russian Federation Federal Medical Research Centre of Psychiatry and Narcology, Moscow, Russian Federation.
Zinaida I
ZI
Storozheva
Federal State Budgetary Scientific Institution, P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russian Federation.
Marina A
MA
Gruden
Federal State Budgetary Scientific Institution, P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russian Federation.
Andrey T
AT
Proshin
Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK sewell@cardiff.ac.uk.
Robert D E
RD
Sewell
D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D000069077:Memory Consolidation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects*; D013830:Thiadiazoles / Q000494:pharmacology*
C494356:4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; D013830:Thiadiazoles; D038362:Glycogen Synthase Kinase 3
TDZD-8; Visuospatial memory; consolidation/reconsolidation; glucose synthase kinase-3 inhibition; learning ability