Hippocampal synapsin I, growth-associated protein-43, and microtubule-associated protein-2 immunoreactivity in learned helplessness rats and antidepressant-treated rats.
Learned helplessness rats are thought to be an animal model of depression. To study the role of synapse plasticity in depression, we examined the effects of learned helplessness and antidepressant treatments on synapsin I (a marker of presynaptic terminals), growth-associated protein-43 (GAP-43; a marker of growth cones), and microtubule-associated protein-2 (MAP-2; a marker of dendrites) in the hippocampus by immunolabeling. (1) Learned helplessness rats showed significant increases in the expression of synapsin I two days after the attainment of learned helplessness, and significant decreases in the protein expression eight days after the achievement of learned helplessness. Subchronic treatment of naïve rats with imipramine or fluvoxamine significantly decreased the expression of synapsin I. (2) Learned helplessness increased the expression of GAP-43 two days and eight days after learned helplessness training. Subchronic treatment of naïve rats with fluvoxamine but not imipramine showed a tendency to decrease the expression of synapsin I. (3) Learned helplessness rats showed increased expression of MAP-2 eight days after the attainment of learned helplessness. Naïve rats subchronically treated with imipramine showed a tendency toward increased expression of MAP-2, but those treated with fluvoxamine did not. These results indicate that the neuroplasticity-related proteins synapsin I, GAP-43, and MAP-2 may play a role in the pathophysiology of depression and the mechanisms of antidepressants.
Iwata
M
M
Department of Neuropsychiatry, Faculty of Medicine, Tottori University, 36-1 Nishi-machi, Yonago, Tottori 683-8504, Japan.
Shirayama
Y
Y
Ishida
H
H
Kawahara
R
R
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D016666:Fluvoxamine / Q000494:pharmacology; D019922:GAP-43 Protein / Q000378:metabolism*; D006380:Helplessness, Learned; D006624:Hippocampus / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016704:Synapsins / Q000378:metabolism*; D013997:Time Factors
D000928:Antidepressive Agents; D019922:GAP-43 Protein; D008869:Microtubule-Associated Proteins; D016704:Synapsins; D016666:Fluvoxamine; D007099:Imipramine