Central noradrenergic depletion by DSP-4 prevents stress-induced memory impairments in the object recognition task.
Environmental stress produces adverse affects on memory in humans and rodents. Increased noradrenergic neurotransmission is a major component of the response to stress and noradrenaline (NA) plays an important role in modulating processes involved in learning and memory. The present study investigated the effect of NA depletion on stress-induced changes on memory performance in the mouse. Central NA depletion was induced using the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP-4) and verified by high performance liquid chromatography (HPLC). A novel cage stress procedure involving exposure to a new clean cage for 1 h per day, 4 days per week for 4 weeks, was used to produce stress-induced memory deficits measured using the object recognition task. 50 mg/kg DSP-4 produced large and sustained reductions in NA levels in the frontal cortex and hippocampus measured 24 h, 1 week and 5 weeks after treatment. Four weeks of exposure to novel cage stress induced a memory deficit in the object recognition task which was prevented by DSP-4 pre-treatment (50 mg/kg 1 week before the commencement of stress).These findings indicate that chronic environmental stress adversely affects recognition memory and that this effect is, in part, mediated by the noradrenergic stress response. The implication of these findings is that drugs targeting the noradrenergic system to reduce over-activity may be beneficial in the treatment of stress-related mental disorders such as post-traumatic stress disorder or anxiety in which memory is affected.
Scullion
G A
GA
Queen's Medical Centre, School of Biomedical Sciences, Institute of Neuroscience, University of Nottingham Medical School, Nottingham, NG7 2UH, UK.
Kendall
D A
DA
Sunter
D
D
Marsden
C A
CA
Pardon
M-C
MC
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D004777:Environment; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009483:Neuropsychological Tests; D009638:Norepinephrine / Q000378:metabolism*; D011897:Random Allocation; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism; D013997:Time Factors
D018663:Adrenergic Agents; D001596:Benzylamines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C012102:DSP 4; D009638:Norepinephrine