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Eur J Pharmacol ; 594(1-3): 109-16, 2008 Oct 10.
Article in English | MEDLINE | ID: mdl-18675266

ABSTRACT

Previous research has suggested that mobilization of neurotrophic factors, such as insulin-like growth factor I (IGF-I), can be involved in the effects of antidepressant treatments. The current experiments showed that IGF-I leads to antidepressant-like effects in the modified rat forced swim test when tested 3 days, but not 1 day, after i.c.v. administration. These effects were sustained longer than the antidepressants paroxetine and desipramine. In addition, blockade of the IGF-I receptor with the IGF-I antagonist JB1 30 min before IGF-I administration prevented the antidepressant-like effects of IGF-I. However, when JB1 was administered 3 days after IGF-I administration and 30 min prior to testing, the antidepressant-like effects of IGF-I were still present suggesting that IGF-1 produces a long-term activation of neural systems involved in the antidepressant response. Because the pattern of antidepressant-like effects of IGF-I resembled those of selective serotonin reuptake inhibitors, the role of serotonin in the behavioral effects of IGF-I was studied. Depletion of serotonin, by the tryptophan hydroxylase inhibitor para-chlorophenylalanine, blocked the antidepressant-like effects of IGF-I. Administration of IGF-I increased basal serotonin levels in the ventral hippocampus and altered the effects of acute citalopram. IGF-I administration did not change hippocampal cell proliferation at the 3-day timepoint when behavioral effects were seen. In addition, IGF-I did not alter the expression of mRNA levels of tryptophan hydroxylase or SERT in the brain stem, or [3H] citalopram binding in the hippocampus or cortex. Thus, IGF-I administration initiates a long-lasting cascade of neurochemical effects involving increased serotonin levels that results in antidepressant-like behavioral effects.


Subject(s)
Antidepressive Agents , Behavior, Animal/drug effects , Insulin-Like Growth Factor I/pharmacology , Serotonin/physiology , Synaptic Transmission/drug effects , Animals , Antidepressive Agents, Second-Generation/pharmacology , Antidepressive Agents, Tricyclic/pharmacology , Binding, Competitive/drug effects , Cell Proliferation/drug effects , Citalopram/metabolism , Dentate Gyrus/cytology , Dentate Gyrus/drug effects , Desipramine/pharmacology , Hippocampus/drug effects , Hippocampus/metabolism , Male , Nerve Growth Factors/pharmacology , Paroxetine/pharmacology , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley , Receptor, IGF Type 1/drug effects , Selective Serotonin Reuptake Inhibitors/metabolism , Swimming/psychology , Tryptophan Hydroxylase/metabolism
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