Post-training down-regulation of memory consolidation by a GABA-A mechanism in the amygdala modulated by endogenous benzodiazepines.
In rats, amygdala benzodiazepine-like immunoreactivity decreases by 29% immediately after the animals step down from the platform of an inhibitory avoidance apparatus and decreases by a further 45% immediately after they receive a training footshock. The decrease is attributable to a release of diazepam or diazepam-like molecules. The immediate post-training intraamygdala injection of the central benzodiazepine antagonist flumazenil (10 nmole/amygdala) causes memory facilitation, and that of the GABA-A agonist muscimol (0.005 to 0.5 nmole) causes retrograde amnesia. Pretraining ip flumazenil administration (2.0 and 5.0 mg/kg) attenuates the effect of post-training muscimol by a factor of at least 100. The higher dose of pretraining flumazenil also causes memory facilitation. The data suggest that post-training consolidation is down-regulated by a GABA-A mechanism in the amygdala modulated by endogenous benzodiazepines released during training and at the time of consolidation.
Izquierdo
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I
Departamento de Bioquimica, Instituto de Biociencias, UFRGS, Porto Alegre, RS, Brazil.
Da Cunha
C
C
Huang
C H
CH
Walz
R
R
Wolfman
C
C
Medina
J H
JH
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001143:Arousal / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001569:Benzodiazepines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000502:physiology; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology*
D011963:Receptors, GABA-A; D001569:Benzodiazepines; D009118:Muscimol; D005442:Flumazenil