Contribution of the dopaminergic system to the effect of chronic fluoxetine in the rat forced swim test.

Abstract

Chronic administration of selective serotonin reuptake inhibitors (SSRI) enhances dopaminergic activity. However, the role of enhanced dopaminergic transmission in the therapeutic effects of this kind of antidepressants is still unclear. Drugs producing dopaminergic activation lead to an increment in general activity. Thus, it is reasonable to assume that some of the therapeutic effects of SSRIs are due to dopaminergic enhanced functionality. The forced swim test (FST) is a widely used test in the screening of new compounds with potential antidepressant activity. In this study the effects of pretreatment with low doses of the DA release inductor cocaine and the D2, D3 and D4 antagonist haloperidol were analyzed in the FST on rats submitted to chronic intragastric administration of the SSRI fluoxetine. Our results show that animals treated with fluoxetine and pre-treated with cocaine had significantly higher latencies than saline or haloperidol pre-treated subjects. Among both fluoxetine and saline treated animals, those pre-treated with cocaine had significant lesser immobility time. Haloperidol pre-treated animals had significantly higher immobility time than those pre-treated with saline. From these results, it is clear that the pharmacological modification of dopaminergic systems leads to behavioral changes in rats treated with both saline and fluoxetine. The FST does not have enough precision as to distinguish between dopaminergic and nondopaminergic components in the antidepressant effects of SSRIs, for this reason the use of the FST in combination to other models is mandatory.

Neuroprotective Effect of Piracetam and Vincamine in a Rat Model of Haloperidol-induced Parkinson's Disease

“…Rats with PD showed depressive-like behavior, as evidenced by increased immobility time of swimming test, when compared with normal animals. In fact, depression associates dopaminergic system dysfunction [29] that was indicated in the present study by the presence of negative correlation between striatal dopamine and immobility time of swimming test. An antidepressive effect was exerted by piracetam or vincamine, which is probably due to their neuroprotective effect, as evidenced by improvement in GDNF and increasing dopamine level in the striatal tissue.…”

Effect of nicotine on serotonin (5-HT) levels in brain of depressed rats

“…Laura A Leon suggested that for the sake of precision in animal modeling, animal models like active avoidance, social isolation, learned helplessness, behavioral despair, genetic depression models would be important to evaluate the antidepressant activity of a new potential compound. 18 Social isolation stress is a valuable stress paradigm for investigating the effects of chronic psychosocial stress on various pathophysiological alterations in animals. 19 Therefore, we conducted this study that compared the effects of imipramine, a tricyclic antidepressant and nicotine.…”

Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish

“…It suggests that SRT generates an anxiolytic effect during the light period [97]. In line with these findings, acute treatment with antidepressants also could increase locomotor activity [98] and reduce the immobility time in rats [99]. Some prior studies also demonstrated hyperactivity in mice with reducing immobility time and an increase in escape behavior after treatment with serotonergic and noradrenergic antidepressants [100,101].…”