Journal
PSYCHOPHARMACOLOGY
Volume -, Issue -, Pages -Publisher
SPRINGER
DOI: 10.1007/s00213-023-06453-0
Keywords
Barnes maze; Spatial memory; Retrieval; Behavioral flexibility; Hippocampus; DSP-4; HPLC; Norepinephrine; Sex; Female
Categories
Ask authors/readers for more resources
This study investigated the contribution of norepinephrine on different phases of spatial memory processing by depleting norepinephrine in the brain. The results showed that the depletion of norepinephrine had only a modest impact on spatial learning and behavioral flexibility, but had a sex-specific effect on memory retrieval and early reversal learning.
RationaleThe contribution of norepinephrine on the different phases of spatial memory processing remains incompletely understood. To address this gap, this study depleted norepinephrine in the brain and then conducted a spatial learning task with multiple phases.MethodsMale and female Wistar rats were administered 50 mg/kg/i.p. of DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) to deplete norepinephrine. After 10 days, rats were trained on a 20-hole Barnes maze spatial navigation task for 5 days. On the fifth day, animals were euthanized and HPLC was used to confirm depletion of norepinephrine in select brain regions. In Experiment 2, rats underwent a similar Barnes maze procedure that continued beyond day 5 to investigate memory retrieval and updating via a single probe trial and two reversal learning periods.ResultsRats did not differ in Barnes maze acquisition between DSP-4 and saline-injected rats; however, initial acquisition differed between the sexes. HPLC analysis confirmed selective depletion of norepinephrine in dorsal hippocampus and cingulate cortex without impact to other monoamines. When retrieval was tested through a probe trial, DSP-4-improved memory retrieval in males but impaired it in females. Cognitive flexibility was transiently impacted by DSP-4 in males only.ConclusionsDespite significantly reducing levels of norepinephrine, DSP-4 had only a modest impact on spatial learning and behavioral flexibility. Memory retrieval and early reversal learning were most affected and in a sex-specific manner. These data suggest that norepinephrine has sex-specific neuromodulatory effects on memory retrieval with a lesser effect on cognitive flexibility and no impact on acquisition of learned behavior.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available