TITLE:
Behavioral Characteristics of Pharmacologically Selected Lines of Rats: Relevance to Depression
AUTHORS:
Darin J. Knapp, Lynette C. Daws, David H. Overstreet
KEYWORDS:
Diisopropylfluorophosphate (DFP), 8-Hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), Flinders Sensitive Line (FSL), Flinders Resistant Line (FRL) Rats, High and Low 8-OH-DPAT Sensitive (HDS & LDS) Rats, Muscarinic Receptors, 5-HT1A Receptors, Forced Swim Test, Social Interaction Test, Elevated Plus Maze, Depression, Anxiety
JOURNAL NAME:
World Journal of Neuroscience,
Vol.4 No.3,
June
17,
2014
ABSTRACT:
This brief review
discusses the behavioral consequences of two pharmacologically selected lines
of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats
were selected on the basis of differential hypothermic and behavioral responses
to the anticholinesterase, diisopropylfluorophosphate (DFP). FSL rats are more
sensitive to the hypothermic effects of cholinergic, serotonergic, and
dopaminergic agonists but less sensitive to the locomotor or stereotypic
effects of dopamine agonists. FSL rats exhibit greater immobility in the forced
swim test and reduced social interaction compared with FRL rats, but do not
differ in saccharin intake, behavior in the elevated plus maze, or responses
for rewarding brain self-stimulation. The exaggerated immobility and reduced
social interaction are counteracted by chronic treatment with antidepressants. Because FSL rats were more sensitive to 5-HT1A
receptor agonists, high (HDS) and low (LDS) 8-OH-DPATsensitive lines
were selectively bred for differential hypothermic responses to the 5-HT1A receptor
agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). HDS rats were also
more sensitive to the hypothermic effects of oxotremorine, a cholinergic
agonist, but selection for this response did not diverge with later selection. HDS
rats exhibited greater immobility in the forced swim test than LDS rats and
this correlated response could be seen early in selection (generation 3). HDS
rats also showed reduced social interaction compared to LDS rats, but did not
differ in behavior in the elevated plus maze. These findings confirm that
selection for hypothermic responses to pharmacological agents do have
behavioral consequences, notably the production of depressive-like phenotypes,
which can be counteracted by chronic antidepressant treatment. Because
increased 5-HT1A receptor sensitivity was common to both selected lines (FSL
and HDS), neurobiological processes dependent on this receptor could contribute
to the abnormal behaviors that manifest in these rat lines and thus suggesting
a mechanism underlying depressive behaviors in humans. However, available human
data are inconsistent with this hypothesis and suggest that other mechanisms
underlie these behavioral abnormalities in HDS and FSL rats. These mechanisms
as well as additional behavioral testing in these rat lines will be discussed.