Reduced cortical noradrenergic neurotransmission is associated with increased neophobia and impaired spatial memory in aged rats.
In the present study, young (5-month-old (mo)) and aged (24 mo) adult male Fischer-344 (F344) rats were assigned to experimental groups based upon their performance of a reference memory task in the Morris water maze and reactivity to a novel palatable taste in a gustatory neophobia task. Levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) were assayed via high performance liquid chromatography (HPLC) in brain regions associated with the locus coeruleus (LC)-hippocampus-cortex system and A1/A2-hypothalamic system. Binding of ligands specific for alpha-1, alpha-2, beta-1, and beta-2 receptors was assessed in hippocampus and cortex with receptor autoradiography. Impaired acquisition and retention of the water maze task and gustatory neophobia in aged rats was primarily associated with decreased NE activity in cingulate cortex (CC) as indicated by a significant reduction in the MHPG/NE ratio coupled with increased NE content. No significant changes in adrenergic receptor binding were detected in any region sampled. The results suggest that an aging-related reduction in cortical NE neurotransmission is associated with the expression of increased neophobia and deficits in spatial learning and memory performance occurring with advanced age in rats.
Collier
Timothy J
TJ
Department of Neurological Sciences, Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, Tech 2000, Suite 200, 2242 W. Harrison St., Chicago, IL 60612, USA. tcollier@rush.edu
Greene
James G
JG
Felten
David L
DL
Stevens
Suzanne Y
SY
Collier
Kathy Steece
KS
D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics; D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics; D000375:Aging / Q000502:physiology*; D000818:Animals; D001345:Autoradiography; D001362:Avoidance Learning; D001522:Behavior, Animal; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000378:metabolism / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000493:pharmacokinetics; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D020120:Iodocyanopindolol / Q000493:pharmacokinetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology*; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010698:Phobic Disorders / Q000503:physiopathology*; D011224:Prazosin / Q000493:pharmacokinetics; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D013028:Space Perception / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D008734:Methoxyhydroxyphenylglycol; D020120:Iodocyanopindolol; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin