On Tue, 03 Mar 2009 21:10:35 -0800, David Epstein wrote: [snip] >A different water test, called the forced-swimming test, is used as a >behavioral assay for antidepressants. The major difference is that >there's no hidden platform to learn about in the forced-swimming >test. There's just...swimming.
I would like to thank David for clarifying which test was being referred to in the Dirk Wittenborn article. More below. >HOWEVER, I've never seen any reference to a forced-swimming test in >which rodents were permitted to drown (or weighted down so they would >do so!). In a brief Google Scholar search, I found that all >references to drowning were in the context of specifying that the >rodents were RESCUED if they seemed to be about to drown: >< http://scholar.google.com/scholar?q=drown++forced+swimming+antidepressant > >I didn't check all 1,290 hits, but I'll be (negatively) impressed if >anyone finds one in which the rodents weren't rescued. I didn't check the 1,290 hits on Google Scholar but I did go over to Pubmed.gov and search there. There is an keyword for "drowned animals" but, used as a text word, does not appear in an article on depression. However, I did find some useful references. The first use of the forced-swimming test appears to reported in an letter in the journal Nature: |R. D. PORSOLT, M. LE PICHON & M. JALFRE |Depression: a new animal model sensitive to antidepressant treatments |Nature 266, 730 - 732 (21 April 1977); doi:10.1038/266730a0 | |A MAJOR problem in the search for new antidepressant drugs is the lack |of animal models which both resemble depressive illness and are selectively |sensitive to clinically effective antidepressant treatments. We have been |working on a new behavioural model in the rat which attempts to meet |these two requirements. The method is based on the observation that a rat, |when forced to swim in a situation from which there is no escape, will, after |an initial period of vigorous activity, eventually cease to move altogether |making only those movements necessary to keep its head above water. |We think that this characteristic and readily identifiable behavioural immobility |indicates a state of despair in which the rat has learned that escape is |impossible and resigns itself to the experimental conditions. This hypothesis |receives support from results presented below which indicate that immobility |is reduced by different treatments known to be therapeutic in depression |including three drugs, iprindole, mianserin and viloxazine which although |clinically active1?3 show little or no 'antidepressant' activity in the usual |animal tests4?6. The critical sentence above is that the rat will stop vigorous activity and only use those movements necessary to keep its head above water. I assume that only if a research leaves the animal in the pool of water indefinitely, it will ultimately drown but there is nothing inherent in dropping the animal into the pool that should cause it to drown (i.e., rats can swim) The Porsolt et al (1977) letter is cited by Cryan et al (2008) as the source for forced swimming test (FST): John F. Cryan, Rita J. Valentino, Irwin Lucki, Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test, Neuroscience & Biobehavioral Reviews, Volume 29, Issues 4-5, Animal Models of Depression and Antidepressant Activity, 2005, Pages 547-569, ISSN 0149-7634, DOI: 10.1016/j.neubiorev.2005.03.008. The Cryan et al article reviews the use of the FST, its predictive validity (i.e., if an antidepressant causes greater activity in a swimming animal, will it have an antidepressant effect in humans with depression), and what neourobiological mechanisms might be involved. There is only one mention of drowning and I quote the relevant text below: |Another controversial argument is that the most obvious solution to the |FST is to be passive and wait for removal from the water and behavior |in the FST has been described as learned immobility (Jefferys and Funder, |1994, West, 1990 A.P. West, and De Pablo et al., 1989). However, this |view oversimplifies the FST situation from an anthropomorphic perspective. |The experimental situation is usually a novel experience for the subject, and |the absence of a solution is not obvious from the beginning of the test given |the potential life-threatening circumstances. The rewards and risks balance |active exploration, that can lead to early escape or exhaustion, with behavioral |immobility, that prolongs survival but leads to certain drowning without rescue. |The difficulty of the strategic choice is illustrated by the diversity of strategies |adopted by wild rats to prolonged forced swimming (Richter, 1957). The role |of learned immobility in the FST is not supported by the expected negative |relationship between greater FST immobility and adrenohormone secretion |(Dal-Zotto et al., 2000 and Rittenhouse et al., 2002). Furthermore, antidepressants |can reduce immobility in a single test session without a pretest after chronic |administration in rats (Overstreet et al., 2004) or after acute administration in |mice (Borsini and Meli, 1988), suggesting that learning to be immobile does |not play a role in the behavioral effects of antidepressants. So, drowning the animal is neither a common or expected outcome. Perhaps Dirk Wittenborn needs to provide a "correction". -Mike Palij New York University [email protected] --- To make changes to your subscription contact: Bill Southerly ([email protected])
