Diabetes Attenuates the Antidepressant-Like Effect Mediated by the Activation of 5-HT1A Receptor in the Mouse Tail Suspension Test

Abstract

Several lines of evidence have indicated that the prevalence of depression in diabetic subjects is higher than that in the general population, however, little information is available on the effects of antidepressants in diabetes. In the present study, the antidepressantlike effect mediated by the activation of 5-HT 1A receptors was examined using the tail suspension test in streptozotocin-induced diabetic mice. Long-lasting increases in 5-HT turnover rates were observed in the diabetic mouse midbrain and frontal cortex, but not in the hippocampus. Duration of immobility was significantly longer in diabetic than in nondiabetic mice in the tail suspension test. The 5-HT 1A receptor agonist ( 7 )-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (3-30 mg/kg, i.p.) reduced the duration of immobility in nondiabetic mice, and this effect was completely antagonized by pretreatment with, a selective 5-HT 1A receptor antagonist. In contrast, 8-OH-DPAT (3 mg/kg-3 mg/kg, i.p.) was ineffective in diabetic mice. The selective 5-HT reuptake inhibitor fluoxetine (3-56 mg/kg, i.p.) reduced the duration of immobility in both nondiabetic and diabetic mice. However, fluoxetine was less effective in diabetic mice than in nondiabetic mice. WAY-100635 (30 mg/kg, s.c.) reversed the suppression of the duration of immobility by fluoxetine (30 mg/kg, i.p.) in nondiabetic mice. On the other hand, the anti-immobility effect of fluoxetine (56 mg/kg, i.p.) was not antagonized by WAY-100635 (30 mg/kg, s.c.) in diabetic mice. The selective 5-HT 2 receptor antagonist 6-methyl-1-(1-methylethyl)-ergoline-8b-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY53,857) (30 mg/kg, s.c.) reversed the anti-immobility effect of fluoxetine in both nondiabetic and diabetic mice. Spontaneous locomotor activity in diabetic mice was not different from that in nondiabetic mice. 8-OH-DPAT (30 mg/kg, i.p.), but not fluoxetine, increased the spontaneous locomotor activity in both nondiabetic and diabetic mice. The number of 5-HT 1A receptors in the mouse frontal cortex was unaffected by diabetes. Plasma corticosterone levels in diabetic mice were significantly higher than that in nondiabetic mice. These results suggest that the antidepressant-like effect mediated by 5-HT 1A receptors may be attenuated by diabetes.

Potentiation of the Antidepressant-Like Effect of Fluoxetine by Aripiprazole in the Mouse Tail Suspension Test

“…had no significant effect on the duration of immobility in the tail suspension test in mice, which is consistent with our previous reports (8,9). Aripiprazole (0.3 mg / kg, i.p.)…”

“…These metabolic changes strongly limit the use of these class of atypical antipsychotic drugs. Since aripiprazole might be an important therapeutic option for treatment-resistant depressive disorders due to its favorable side-effect profile, we investigated the effect of aripiprazole alone or in combination with the sub-effective dose of fluoxetine (8,9) on the duration of immobility in the mouse tail suspension test. Moreover, we also examined the influence of aripiprazole on glucose metabolism.…”

“…The sub-effective dose of fluoxetine (10 mg / kg, i.p.) was based on our previous studies using the mouse tail suspension test (8,9). The dose of aripiprazole at 0.3 mg/ kg was according to the previous study (10).…”

The Antidepressant-Like Action of Metabotropic Glutamate 7 Receptor Agonist N,N′-Bis(Diphenylmethyl)-1,2-Ethanediamine (AMN082) Is Serotonin-Dependent

“…5-HT1A and 5-HT2A receptors have been shown to play a crucial role in the regulation of serotonergic neurotransmission and the mechanism of action of several ADs, including SSRIs, monoamine oxidase inhibitors, and tricyclics (Middlemiss et al, 2002;Hensler, 2006). Furthermore, pretreatment with antagonists of 5-HT1A and 5-HT2A receptors has been shown to antagonize the action of the SSRIs in the TST in mice (Miyata et al, 2004). Thus, we examined the influence of the pretreatment of mice with the 5-HT1A receptor antagonist WAY100635 (Forster et al, 1995) and the 5-HT2A/2C receptor antagonist ritanserin (Hoyer et al, 1994) by using TST.…”

Effect of Metabolic Syndrome on Depression in Mice

“…46,47 Animal models of type 2 diabetes associated depression also shows similar characteristics. 48 The effect of NE on diabetes associated depression is far from being clear. Some studies, have reported a change in NE concentration in both depressed and diabetic animals.…”