I do not have a direct answer to your question, sorry - never tried it in rat behavioral models.

Do you think your observations can be accounted for by SSRI MOA of fluoxetine? As you probably are aware of, it can also block voltage-gated sodium channels in the therapeutic range of concentrations, i.e.: The Mechanism of Activity-Dependent Sodium Channel Inhibition by the Antidepressants Fluoxetine and Desipramine

N. Lenkey,R. Karoly,J. P. Kiss,B. K. Szasz,E. S. Vizi andA. MikeMolecular Pharmacology December 2006 vol. 70 no. 6 2052-2063.

Just a thought towards potential explanation of your observations... 

I also do not have a direct answer, but there is a 1992 review that states that fluoxetine leads to a "decrease in food intake beginning with the first dose and a decrease in body weight or in weight gain after multiple doses" (see http://www.ncbi.nlm.nih.gov/pubmed/1728830). Perhaps the immobility is a result of the severe reduction in energy intake prior to testing?

Thank you for the answers, Jessica and Victor.  I have the Yen & Fuller article in hand, and it is very helpful.  I agree that the reduction of immobility is the result of reduced energy intake.  The fluoxetine rats were noticeably tired, almost lethargic-like compared to saline-treated rats.  Also, they noticeably ate and drank less food and water.  It just seems very odd to me coming from such a well-established antidepressant that is supposed to decrease immobility, not increase it....almost as if too much of a good thing is a bad thing.

1) We observed silimar weight loss in rats after chronic (5 weeks) fluoxetine in chronic mild stress model several years ago. We assumed that at least in part it was an effect of diarrhoea.

2) In case of SSRIs you should use the modified Porsolt test; see e.g.  http://www.if-pan.krakow.pl/pjp/pdf/2007/6_785.pdf

I think... after sometime the animals learned stop swimming because this will not help them. Even the control or test groups.

Thank you for the insight, Piotr and Erich.  The learned immobility that you speak of is a possibility.  Piotr, do you recall the dose of fluox and route of administration?  Thank you.

David, it was 10 mg/kg ip

I am not sure if in that particular experiment the other nonspecific reason of weight loss was not involved

fluoxetin increases serotonin signaling in brain.

serotonin decreases appetite in arcuate nucleus by inhibiting hunger-related neurons and activating satiety-related neurons.

serotonin increases output of ventral ACC, which signals satisfaction, safety and well-being (gains and wins, reaching the comfort zone). so with higher serotonin levels we feel more full, comfortable, at ease, thus opposit of deprived.

serotonin also inhibits motivation and drive (to go after food or other rewards) by supressing output of D1 loop of ventral striatum, so people and animals move less for  the valuable rewards and goals.

in https://www.scienceopen.com/document/vid/13e62385-1fb0-4a49-9a5d-e435baa5b95e/review/964ece93-cdbe-415d-bb5f-939f6732d514?0#author-and-article-info

Do the rats have rigid posture and serotonin syndrome?

PMID:

17823767

Well, may be such effects of fluoxetine are not so strange if you take in account that  has been used for reducing the appetite in humans. In this sense point, also, "adverse reactions" such as akathisia and other movement disorders (incidentally, recognized in the DSM-IVtr), and apathy or emotional blunting, these drugs approaching of another group: antipsychotics.

I've studied the effects of fluoxetine on food intake and locomotion at acute doses of 1, 3 and 10 mg/kg i.p. The doses 3 and 10 mg/kg significantly reduce food intake and 10 mg/kg markedly reduced activity for >4 hours. I'd say 10 mg/kg i.p. is very anorectic and sedative dose, it most likely can increase immobility in the FST due to the sedation. Fluoxetine also has an active, slowly-metabolizing metabolite (norfluoxetine) which will increase the anorectic and sedative effects with repeated administration like the one you used. Hope this helps. :)

Some refs with e.g. fluoxetine 10 mg/kg ip and reduced food intake:

Wong, D.T., Reid, L.R., Threlkeld, P.G., 1988. Suppression of food intake in rats by fluoxetine: comparison of enantiomers and effects of serotonin antagonists. Pharmacol Biochem Behav 31, 475-479;

Halford, J.C., Blundell, J.E., 1996. Metergoline antagonizes fluoxetine-induced suppression of food intake but not changes in the behavioural satiety sequence. Pharmacol Biochem Behav 54, 745-751.

Halford, J.C., Harrold, J.A., Boyland, E.J., Lawton, C.L., Blundell, J.E., 2007. Serotonergic drugs : effects on appetite expression and use for the treatment of obesity. Drugs 67, 27-55.

Hi David, here at my research group a girl worked with fluoxetine and had a lot of adverse effect. Write to her ([email protected]) and you can share experiences.

Good luck

Thank you all very much for your responses!  I have been away from ResearchGate for a while so I apologize if my absence came off as rude.

Matthew, we did notice our rats display somewhat of a hind limb abduction immediately following injections, as well as a decreased motivation to eat and a large decrease in locomotor activity in general, reflecting a sort of an apathetic state. 

Based on everyone's responses here, I feel a little better.  It is frustrating when you read papers that suggest 20 mg/kg to be used as a positive control in the forced swim test to increase swimming and decrease immobility, and then when you implement those procedures you find something exactly opposite (increased immobility and "depressive-like states").

Regardless, based on our observations, fluoxetine did indeed have an anorectic effect that led to such intense food intake suppression and decreased energy, leading to the atypical increases in immobility.  It is a hard sell, though.

Thanks again so much for all of your responses, I greatly appreciate your willingness to add your insight.

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