Impairment of contextual fear conditioning in rats by Group I mGluRs: reversal by the nootropic nefiracetam.
The blockade of Group I metabotropic glutamate receptors (mGluRs) may be a potential strategy for prevention therapy of neurotoxicity. We here confirm previous reports that systemic application of the Group I antagonist, 1-aminoindan-1,5-dicarboxylic acid (AIDA), causes amnesia in a contextual fear conditioning paradigm in rats. This deficit was fully reversed by long-term pretreatment with the nootropic nefiracetam, which in fact obtained supranormal performance. Our data suggest that application of Group I antagonists to prevent neurotoxicity, combined with nootropic treatment to prevent cognitive deficits, may be a therapeutic strategy for the development of novel antineurotoxic treatments.
Department of Biomedical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK. g.riedel@abdn.ac.uk
Gernot
G
Riedel
Karin
K
Sandager-Nielsen
Euan M
EM
Macphail
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000187:drug effects* / Q000523:psychology*; D007189:Indans / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
C095756:1-aminoindan-1,5-dicarboxylic acid; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018697:Nootropic Agents; D011760:Pyrrolidinones; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C058876:nefiracetam