Extinction-induced "despair" in aged and adult rats: links to neurotrophins in frontal cortex and hippocampus.
In the search for animal models of human geriatric depression, we found that operant extinction of escape from water results in the expression of immobility in different age groups, indicative of behavioral "despair", which was also associated with the resistance-to-extinction (RTE) expressed by these animals. With respect to the neurotrophin hypothesis of depression, nerve-growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) protein levels in frontal cortex (FC) and hippocampus (HP) were examined and related to behavioral immobility and RTE in the water maze in aged and adult Wistar rats. Age-related increases in levels of NGF were found in HP and of NT-3 in FC. Indices of immobility showed relationships in the aged with NGF and, in adults, with BDNF, pointing to a dissociation of neurotrophic involvement in extinction trial-induced "despair" in aged and adult rats. The present results support the hypothesis, that extinction-induced immobility in the water maze reflects a state akin to behavioral despair and point to age-related differences of neurotrophic involvement in depressive-like symptoms. The concept of extinction-induced behavioral "despair" in the aged subsumes several aspects of human geriatric depression, such as co-morbidity of learning impairment and anxiety, and, thus could represent a useful paradigm to examine the neuronal mechanisms underlying depression, especially in aged rodents.
Topic
Bianca
B
Institute of Physiological Psychology, University of Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
Huston
Joseph P
JP
Namestkova
Katerina
K
Zhu
Shun-Wei
SW
Mohammed
Abdul H
AH
Schulz
Daniela
D
D000375:Aging / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D046353:Immobility Response, Tonic / Q000502:physiology; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D018709:Statistics, Nonparametric
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020932:Nerve Growth Factor