Name: animal models of depression - chronic despair model (cdm)
Uploaded: 2021-09-23T13:30:00
Description: Watch this Scientific Journal Video about Animal Models of Depression - Chronic Despair Model CDM at JoVE.com

This work was funded by internal funds of the University Clinic Freiburg, Department of Psychiatry and Psychotherapy and the Berta-Ottenstein Program for Clinician Scientists (to SV). TS is funded by the grants of Medical Research Foundation (FRM) (AJE201912009450) and the University of Strasbourg Institute of Advance Studies (USIAS) (2020-035), as well as Centre National de la Recherche Scientifique (CNRS), France.

All experiments were performed in agreement with European guidelines (EU 2010/63) and in accordance with the German animal protection law (TierSchG), FELASA (www.felasa.eu/guidelines.php), the national animal welfare body GV-SOLAS (www.gv-solas.de/index.html) guide for the care and use of laboratory animals, and were approved by the animal welfare committee of the University of Freiburg and by the Comite d&#8217;Ethique en Matiere d&#8217;Experimentation Animale de Strasbourg (CREMEAS, CEEA35), as well as local authoriti...

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The CDM model represents a relevant and established model for testing the anti-depressive potency of new interventions and opens an extended time window for molecular or electrophysiological experiments to elucidate the pathophysiology of depression. Especially when combined with other tests to assess a depression-like state, CDM has a high face and concept validity. It combines subchronic stress and acquired helplessness for induction and produces a long-lasting depressive-like state. It is insensitive to the single app...

Affective disorders, such as major depressive disorder, are among the most frequent and challenging mental illnesses and are associated with high individual suffering1, an increase of suicide risk2, and cause a considerable socioeconomic burden3 for society. Despite its impact, treatment options are limited, and there is an urgent need for the development of novel antidepressive interventions, especially due to the innovation crisis in psychopharmacology over the last decades. In order to understand the pathophysiology of depression and test potential new agents, rational and valid animal models are urgently needed4. For almost half a century, the classical forced swim test (FST), originally described by Porsolt5, was used as induction and read-out for screening of potential novel antidepressants. It consists of a forced swim period for 5-15 min on day 1, subsequent one-time drug application, and evaluation of the portion mice spend immobile in water in another swim period on the following day. The immobility time was considered to represent a missing natural escape behavior and was thought to correlate with the degree of a depression-like state in the mice5.
The classical FST has been heavily criticized, not only in the scientific community6,7,8 but also in public media8. Most controversies around the FST are due to the short induction and treatment periods of only 1 day in the classical paradigm. It was argued that FST represents rather an acute trauma model than a state comparable to human depression. Moreover, the Porsolt test might be suitable as a screening tool for potential antidepressive agents, but it ignores the delayed onset of action of many antidepressants.
The chronic despair model (CDM)9,10,11,12,13,14,15, which is derived from the original FST, represents a more appropriate animal model for depression. In CDM, repeated swim stress over 5 consecutive days avoids acute traumatic effects. By failing to escape from a repeated and ongoing stressful situation, mice are thought to develop a state of helplessness, surrender, and ultimately despair. This paradigm is more comparable to current psychological theories for the development of depression in humans than a single acute trauma, which is commonly experienced at the onset of a posttraumatic stress disorder. The resulting depression-like state in CDM is stable for up to 4 weeks9 and therefore opens the possibility for longer treatment periods, which are better comparable to clinical conditions, where antidepressants usually need 2-4 weeks to show a benefit16.
The evaluation of the depressive-like state should then be multidimensional. The measurement of immobility time, such as in the classical FST, is useful, but should not be used as the only outcome parameter. Various methods, which are described below, should be able to map different dimensions of a depressive state in line with symptoms usually found in depressed humans. Suitable read-out assessments could include escape behavior (immobility time9,10,17), tail suspension test (TST)9, anhedonia (classical sucrose preference test (SPT)18), motivation-oriented behavior (nose-poke sucrose preference test (NPSPT)10), expectation/exploration-behavior (response to ambiguous signal19; Y-maze test9), electrophysiology (measurements of long-term plasticity (long-term potentiation, LTP; long-term depression, LTD)20), molecular assessments (activation patterns of immediate early genes (IEGs); further stress patterns21).
Theoretically, a repeated swim test can be used to induce a depressed state without any assessment of immobility time. However, it is strongly recommended to provide at least a proof-of-concept experimental series with immobility times. Additionally, CDM represents a suitable model to assess the development of a depressive-like state by measuring immobility time during the induction phase. Specific mouse strains or mice treated before swimming can be evaluated with respect to resilience or vulnerability to stress and the induction of behavioral despair.

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	<tbody>
		<tr>
			<td>Beaker, 2000 mL</td>
			<td>Kimble Kimax</td>
			<td>14000-2000</td>
			<td>any vessel &#62;2000ml and diameter of 24-26 cm possible</td>
		</tr>
		<tr>
			<td>Digital Thermometer</td>
			<td>Hanna Instruments</td>
			<td>846-4708</td>
			<td>any digital thermometer possible</td>
		</tr>
		<tr>
			<td>Digitalwaage 200 g Dipse</td>
			<td>DIPSE</td>
			<td>tp200</td>
			<td>any digital scale possible</td>
		</tr>
		<tr>
			<td>Lenovo ThinkCentre V50a-24IMB AiO 11FJ00DVGE - 60,5 cm</td>
			<td>Lenovo</td>
			<td>A 908278</td>
			<td>any standard Personalcomputer possible</td>
		</tr>
		<tr>
			<td>Logitech PTZ Pro</td>
			<td>Logitech</td>
			<td>1000005246</td>
			<td>any high resolution camera possible</td>
		</tr>
		<tr>
			<td>Stopwatch ROTILABO</td>
			<td>Carl Roth</td>
			<td>L423.1</td>
			<td>any stopwatch possible</td>
		</tr>
		<tr>
			<td>Timer ROTILABO</td>
			<td>Carl Roth</td>
			<td>A802.1</td>
			<td>any timer possible</td>
		</tr>
	</tbody>
</table>

animal models of depression - chronic despair model (cdm)

Major depressive disorder is one of the most prevalent forms of mental illnesses and causes tremendous individual suffering and socioeconomic burden. Despite its importance, current pharmacological treatment is limited, and novel treatment options are urgently needed. One key factor in the search for potential new drugs is evaluating their anti-depressive potency in appropriate animal models. The classical Porsolt forced swim test was used for this purpose for decades to induce and assess a depressive-like state. It consists of two short periods of forced swimming: the first to induce a depressed state and the second on the following day to evaluate the antidepressant effect of the agent given in between the two swim sessions. This model might be suitable as a screening tool for potential antidepressive agents but ignores the delayed onset of action of many antidepressants. The CDM was recently established and represented a modification of the classical test with notable differences. Mice are forced to swim for 5 consecutive days, following the idea that in humans, depression is induced by chronic rather than by acute stress. In a resting period of several days (1-3 weeks), animals develop sustained behavioral despair. The standard read-out method is the measurement of immobility time in an additional delayed swim session, but several alternative methods are proposed to get a broader view of the mood status of the animal. Multiple analysis tools can be used targeting behavioral, molecular, and electrophysiological changes. The depressed phenotype is stable for at least 4 weeks, providing a time window for rapid but also subchronic antidepressant treatment strategies. Furthermore, alterations in the development of a depressive-like state can be addressed using this approach. CDM, therefore, represents a useful tool to better understand depression and to develop novel treatment interventions.

In the first swim session of the induction phase of CDM, mice usually show a mean immobility time between 190 s and 230 s, which constantly rises with every additional swim session (Figure 1A). This increase is more pronounced in the first 3 days and reaches a plateau-like phase during the last 2-3 days. The immobility-time measured on day 5 remains stable over up to 4 weeks, indicating stable behavioral despair. The antidepressant potency of an intervention ...

Watch this Scientific Journal Video about Animal Models of Depression - Chronic Despair Model CDM at JoVE.com

Animal Models of Depression - Chronic Despair Model CDM

The chronic despair mouse model (CDM) of depression consists of repetitive forced swim sessions and another delayed swim phase as a read-out. It represents a suitable model for induction of a chronic depressive-like state stable for at least 4 weeks, amendable to evaluate subchronic and acute treatment interventions.

Animal Models of Depression - Chronic Despair Model (CDM)

Major depressive disorder is one of the most prevalent forms of mental illnesses and causes tremendous individual suffering and socioeconomic burden. ...

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