A couple of behavioural pharmacology preclinical screens could be used in which SSRIs are active. Forced swim (Porsolt) test and tail suspension test (in mice) are the classic two. Would be better to quantify that you really only see a serotonin increase and not a noradrenaline / dopamine decrease to show selectivity of the serotonin transporter blockade over that of other amine transporters. Microdialysis with HPLC-ECD would be an option here. SSRIs also are used in OCD like behaviours so reversal of sub-chronic quinpirole induced compulsive checking of objects in the open field is also a possibility. Feel free to contact me if I can further advise.

Great, thanks for giving the connectivity Bio analysis of 5-HT along with DA and NA levels in OCD animal model will be a better screening model. Then how the following statement be addressed in this model upon SSRI treatment? Kindly comment - 5HT increase would be from the blockade of re-uptake transporter but not by promoting the synthetic/ sensitizing pathway?

Yes, SSRIs work not by affecting 5HT synthesis but simply blocking 5HT reuptake keeping synaptic (extracellular) levels higher. This is what microdialysis would measure. I think the best way to behaviourally screen is test in at least 2 tests and those drugs (that block SSRIs) that would work in more than 1 test are more convincing drug candidates to take forward. By the way, why do you want to screen for new SSRIs anyway - there are already many on the market (e.g. fluoxetine and fluvoxamine) so what would be the added value?

I think behavioral effects of antidepressant drugs are quite different from their sole effects on serotonin reuptake, especially after chronic use. Even textbooks like Katzung's Pharmacology begun to explain antidepressant activity mostly depending on increasing neuroplasticity and BDNF levels. Previously, we showed that fluoxetine (and 8-OH-DPAT, selective 5-HT1A agonist) could partially (>50%) substituted for tianeptine (serotonin reuptake increasing antidepressant drug) in drug discrimination procedure in rats. Article Discriminative stimulus properties of tianeptine

Circular movement of animal in forced swimming test?

@ Jeffrey C. Glennon, Best wishes

Because the drug is NCE, how can it be guaranteed that test drug (identified as SSRI) is not involved in the promoting synthesis? and the 5-HT increase is only through re-uptake transporter inhibition. I am looking to demonstrate the mechanism of action (SSRI) and pharmacology (behaviour) in a single experiment.

Not working for a pure SSRI but checking the add on activity.