Selective breeding for increased cholinergic function: development of a new animal model of depression.

Two lines of rats that were selectively bred to vary in their sensitivity to the anticholinesterase DFP exhibited different degrees of behavioral depression after injection of the muscarinic agonist arecoline (2 mg/kg). The line of rats with increased behavioral depression after arecoline (the Flinders sensitive or S-line) also exhibited a greater reduction of activity in an open field chamber following exposure to foot shock and greater immobility in a forced swim test than the line of rats with reduced behavioral depression after arecoline (the Flinders resistant or R-line). In addition, the Flinders S-line exhibited a better memory on an inhibitory avoidance task. These differences were not related to differences in shock sensitivity between the lines. Thus, the Flinders S-line of rats reacts to both mild stressors and a cholinergic agonist with greater behavioral depression and may, therefore, be a useful new animal model of human depressive disorders, one that focuses on cholinergic supersensitivity.