The WAGxDA rat: an animal model of cholinergic supersensitivity.

A heightened response to the muscarinic effects of acetylcholine appears to be involved in many of the symptoms associated with affective disorders. We have developed an animal model for cholinergic supersensitivity to study this involvement in more detail. Our findings on cholinergic supersensitivity and on behavioral despair in this model, the WAGxDA F1 hybrid, are reported here. Female WAGxDA rats show a heightened response to muscarinic agonist in a temperature depression test (TDT) and both males and females show an increased level of inherent despair in a Porsolt swim test; however, this cholinergic supersensitivity does not appear to be based on an increased density or affinity of cholinergic receptors. Other possible mechanisms are discussed.