Amnesia produced by altered release of neurotransmitters after intraamygdala injections of a protein synthesis inhibitor.
Amnesia produced by protein synthesis inhibitors such as anisomycin provides major support for the prevalent view that the formation of long-lasting memories requires de novo protein synthesis. However, inhibition of protein synthesis might disrupt other neural functions to interfere with memory formation. Intraamygdala injections of anisomycin before inhibitory avoidance training impaired memory in rats tested 48 h later. Release of norepinephrine (NE), dopamine (DA), and serotonin, measured at the site of anisomycin infusions, increased quickly by approximately 1,000-17,000%, far above the levels seen under normal conditions. NE and DA release later decreased far below baseline for several hours before recovering at 48 h. Intraamygdala injections of a beta-adrenergic receptor antagonist or agonist, each timed to blunt effects of increases and decreases in NE release after anisomycin, attenuated anisomycin-induced amnesia. In addition, similar to the effects on memory seen with anisomycin, intraamygdala injections of a high dose of NE before training impaired memory tested at 48 h after training. These findings suggest that altered release of neurotransmitters may mediate amnesia produced by anisomycin and, further, raise important questions about the empirical bases for many molecular theories of memory formation.
Canal
Clinton E
CE
Neuroscience Program, Department of Animal Sciences, University of Illinois at Urbana-Champaign, Champaign, IL 61820, USA.
Chang
Qing
Q
Gold
Paul E
PE
D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000647:Amnesia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D000679:Amygdala / Q000187:drug effects* / Q000473:pathology*; D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin; D000841:Anisomycin; D004298:Dopamine; D009638:Norepinephrine