The Flinders Sensitive Line rat: a selectively bred putative animal model of depression.
The Flinders Sensitive Line (FSL) rats were originally selectively bred for increased responses to an anticholinesterase agent. The FSL rat partially resembles depressed individuals because it exhibits reduced appetite and psychomotor function but exhibits normal hedonic responses and cognitive function. The FSL rat also exhibits sleep and immune abnormalities that are observed in depressed individuals. Neurochemical and/or pharmacological evidence suggests that the FSL rat exhibits changes consistent with the cholinergic, serotonergic, dopaminergic, NPY, and circadian rhythm models but not the noradrenergic, HPA axis or GABAergic models of depression. However, evidence for the genetic basis of these changes is lacking and it remains to be determined which, if any, of the neurochemical changes are primary to the behavioral alterations. The FSL rat model has been very useful as a screen for antidepressants because known antidepressants reduced swim test immobility when given chronically and psychomotor stimulants did not. Furthermore, rolipram and a melatonin agonist were shown to have anti-immobility effects in the FSL rats and later to have antidepressant effects in humans. Thus, the FSL rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed individuals and has been very effective in detecting antidepressants.
Overstreet
David H
DH
Department of Psychiatry, Skipper Bowler Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB #7178, Thurston-Bowles Bldg 3009, Chapel Hill, NC 27599-7178, USA. dhover@med.unc.edu
Friedman
Elliot
E
Mathé
Aleksander A
AA
Yadid
Gal
G
D000818:Animals; D000928:Antidepressive Agents / Q000145:classification / Q000627:therapeutic use; D001007:Anxiety / Q000209:etiology; D001249:Asthma / Q000209:etiology; D001526:Behavioral Symptoms / Q000503:physiopathology*; D001947:Breeding / Q000379:methods; D002940:Circadian Rhythm / Q000502:physiology; D003863:Depression / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D004195:Disease Models, Animal; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D007154:Immune System Diseases; D043183:Irritable Bowel Syndrome / Q000209:etiology; D009414:Nerve Growth Factors / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D000928:Antidepressive Agents; D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents