Age-related changes in the antidepressant-like effect of desipramine and fluoxetine in the rat forced-swim test

Abstract

Some reports suggest that older patients are less responsive to antidepressants than young adults, but this idea has not been fully supported. Here, we investigated the role of aging in the behavioral effects of the antidepressants, desipramine (DMI) (5, 10, and 20 mg/kg) and fluoxetine (FLX) (5, 10, and 20 mg/kg) in young adults (3-5 months), middle-aged (MA, 12-15 months), and senescent (SE, 23-25 months) male rats in the forced-swim test. In addition, locomotor activity and motor coordination were assessed as side-effects. DMI and fluoxetine produced an antidepressant-like effect in YA and MA animals, although in the latter group, a shift to the right in the dose-response curve was found for DMI. Importantly, neither drug was effective in SE animals. Motor side-effects were produced mainly by DMI in MA and SE rats. Therefore, a decrease in the antidepressant-like effect is associated strongly with senescence as well as an increased vulnerability to motor side-effects, particularly of tricyclics. This study is significant because SE animals are scarcely studied in pharmacological screening tests, and our findings might be useful for improving antidepressant treatments for the increasing aged population.

The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats

“…A similar result was reported by Olivares-Nazario et al . [ 35 ] who showed that senescent (23–25 months) male rats did not respond to the antidepressant-like effect of desimipramine or fluoxetine in the FST. In contrast, middle-aged females (14 to 18 month old), subjected to the chronic mild stress depression model, showed a transitory antidepressant-like effect of 10 mg/kg CIT [ 50 ].…”

“…Interestingly, aging also abbreviates the intervention window with E 2 , since the point of restitution in relation to time after OVX is three months after OVX in young rats, while in aged rats it is restricted to one week [ 13 , 32 , 33 , 34 ]. The action of antidepressants is also modulated by age, because their effect decreases in middle-age rats and may vanish at senescence [ 34 , 35 , 36 ].…”

Effects of Vitamin D3 in Long-Term Ovariectomized Rats Subjected to Chronic Unpredictable Mild Stress: BDNF, NT-3, and NT-4 Implications

“…The dose of fluoxetine was utilized according to earlier experimental data [50]. Several studies have demonstrated that the administration of fluoxetine decreases depressive-like behavior in rodents [50,51]. All drugs were injected subcutaneously (0.1 mL/rat) for the 4 weeks during the CUMS procedure—30 min before the daily stressor action—and throughout the period of the behavioral tests.…”

Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

“…Such antidepressants produce their therapeutic effects through actions on diverse neurotransmitter systems, including the serotonergic, noradrenergic, and dopaminergic systems [ 3 ]. The principal antidepressant drugs are tricyclic antidepressants (e.g., clomipramine and imipramine), monoamine oxidase inhibitors (e.g., phenelzine and selegiline), selective serotonin reuptake inhibitors (e.g., fluoxetine and fluvoxamine), selective dopamine reuptake inhibitors (e.g., amineptine and methylphenidate), selective norepinephrine reuptake inhibitors (e.g., reboxetine and viloxazine), and dual antidepressant drugs (e.g., venlafaxine and duloxetine) [ 4 , 5 ].…”