AMPA receptors mediate passive avoidance deficits induced by sleep deprivation.
The present study addressed the effects of sleep deprivation (SD) on AMPA receptor (AMPAR) binding in brain regions associated with learning and memory, and investigated whether treatment with drugs acting on AMPAR could prevent passive avoidance deficits in sleep deprived animals. [(3)H]AMPA binding and GluR1 in situ hybridization signals were quantified in different brain regions of male Wistar rats either immediately after 96 h of sleep deprivation or after 24h of sleep recovery following 96 h of sleep deprivation. Another group of animals were sleep deprived and then treated with either the AMPAR potentiator, aniracetam (25, 50 and 100mg/kg, acute administration) or the AMPAR antagonist GYKI-52466 (5 and 10mg/kg, acute and chronic administration) before passive avoidance training. Task performance was evaluated 2h and 24h after training. A significant reduction in [(3)H]AMPA binding was found in the hippocampal formation of SD animals, while no alterations were observed in GluR1 mRNA levels. The highest dose of aniracetam (100mg/kg) reverted SD-induced impairment of passive avoidance performance in both retention tests, whereas GYKI-52466 treatment had no effect. Pharmacological enhancement of AMPAR function may revert hippocampal-dependent learning impairments produced after SD. We argue that such effects might be associated with reduced AMPAR binding in the hippocampus of sleep deprived animals.
Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Francisco Paulino
FP
Dubiela
Claudio Marcos
CM
Queiroz
Karin Di Monteiro
KD
Moreira
Jose N
JN
Nobrega
Luciane Valéria
LV
Sita
Sergio
S
Tufik
Debora Cristina
DC
Hipolide
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001569:Benzodiazepines / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007859:Learning Disabilities / Q000150:complications* / Q000378:metabolism*; D008297:Male; D018697:Nootropic Agents / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D012892:Sleep Deprivation / Q000150:complications*; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
D001569:Benzodiazepines; D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D011760:Pyrrolidinones; D018091:Receptors, AMPA; D014316:Tritium; C061950:GYKI 52466; C036466:aniracetam
AMPA receptor; Aniracetam; GYKI-52466; Passive avoidance task; Sleep deprivation