Antidepressant-like behavioral effects of IGF-I produced by enhanced serotonin transmission

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.

Nutritional Aspects of Depression

“…a blockade of peripheral IGF reduces exercise induced neurogenesis [52][53][54][55][56]. Correspondingly, in animal models of rats and mice an antidepressant trial of IGF was comparable with the behavioral effects of serotonergic antidepressants and improved frontal cortex neuroplasticity [53,57].…”

Effects of single-dose ketamine infusion on behavioral parameters and neuronal activation in the medial prefrontal cortex of juvenile rats exposed to prenatal stress

“…[42] The most commonly prescribed antidepressants such as tricyclic anti-depressants and selective serotonin reuptake inhibitors (SSRIs) have significant limitations with delayed onset of action and their effects do not last beyond a few hours following their acute administration. [43] Whereas, effects of ketamine are distinct from those conventional drugs since it produces protracted behavioral effects persisting from one to several days after administration. [29] The majority of studies indicate that the FST remains sensitive to the protracted effects of ketamine up to 1 week after a single injection.…”

Hyperforin promotes mitochondrial function and development of oligodendrocytes

“…A recent study has shown that chronic treatment of fluoxetine increases the levels of both IGF-1 mRNA and IGF-I receptors in the frontal cortex but not the hippocampus in rat brains (Grunbaum-Novak et al, 2008). Furthermore, intracerebroventricular administration of IGF-I has shown antidepressant-like behavioral effects with increased serotonin transmissions in rodent models (Hoshaw et al, 2008). CREB is also highly expressed in oligodendrocytes (SatoBigbee and Yu, 1993;Sato-Bigbee et al, 1994).…”