Metabotropic glutamate receptors (mGluRs) are involved in early phase of memory formation: possible role of modulation of glutamate release.
Metabotropic glutamate receptors (mGluRs) groups I and II are involved in the cellular processes of long-term potentiation (LTP) and learning and memory formation. I.c.v. injection of the mGluRs agonist 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) can impair memory formation in some types of learning task. The role of mGluRs in neurotransmitters release and production of second messengers has been suggested. The aim of the present study was to determine the effect of i.c.v. administration of the new potent mGluRs agonist ABHxD-I and compare its effect with that of ACPD. We studied the effect of both agonists on acquisition and memory for a one-trial passive avoidance learning task in day-old chicks and on the training related glutamate (Glu) release. ACPD or ABHxD-I (50 nmole per chick, i.c.v. injection) were administered at different times before or after training and chicks were tested at various times after training. Chicks injected with ABHxD-I 30 min before training showed amnesia when tested 30 min or 3h after training. The amnestic effect of ACPD was significant only 30 min after training. Glu release evoked by 70 mM KCl was measured in slices prepared from the IMHV of chick brain isolated from animals injected with either ACPD or ABHxD-I 30 min before training and tested 30 min after training. Glu concentration was measured using HPLC. Both ACPD and ABHxD-I significantly increased Glu release in slices isolated from untrained chicks (30 and 48% compare to control, respectively, P<0.05). Training itself increased Glu release (41% compared to control, P<0.01) and no additional effect of either ACPD or ABHxD-I was observed. These results suggest that mGluRs groups I and II are involved in the early stages of memory formation and that application of either of the studied mGluRs agonists may interfere with that process. The amnestic effect of ABHxD-I seems to be stronger and longer lasting. Although the mechanism of this effect still remains unclear, our results suggest that disregulation of Glu release by mGluR agonists may participate in this process.
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland. s.e.salinska@open.ac.uk
Elzbieta
E
Salinska
Aleksandra
A
Stafiej
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002645:Chickens; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D007858:Learning; D008297:Male; D008568:Memory; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism / Q000502:physiology*
C112101:2-aminobycyclo(2.1.1)hexane-2,5-dicarboxylic acid; D001643:Bridged Bicyclo Compounds; D003998:Dicarboxylic Acids; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid