Manipulation of behavioral disorders in autoimmune mice via prolactin

Autoimmune mice perform poorly in two-way active avoidance tasks, and the extent of this performance deficit appears to be related to the extent of autoimmunity following developmental manipulations. In the current study, the pituitary hormone prolactin, which has immune-enhancing effects, was used to manipulate this behavioral disorder in adulthood. Prolatinergic manipulation may be achieved by the use of dopaminergic drugs. In two experiments, autoimmune NZB X NZW F1 (BW) mice received either pimozide (PIM; a D2 antagonist) or bromocriptine (CB154; a dopamine agonist) in their drinking water. Control subjects received plain water. Following treatment, subjects were tested in an activity monitor, and active avoidance learning. Circulating PRL levels, as measured by RIA, were significantly increased by PIM and significantly decreased by CB154. Neither drug affected circulating levels of autoantibodies to DNA or cardiolipin, a phospholipid. In Experiment 1, in which mice were tested at 12 weeks of age, after 6 weeks of drug treatment, PIM treated animals of both sexes showed significantly more failures to escape the shock in avoidance conditioning, while CB154 did not have significant effects. In Experiment 2, in which mice were tested at 16 weeks of age, after 12 weeks of drug treatment, CB154 treated females (males were not tested) showed significantly fewer failures to escape, while PIM did not have significant effects. The effects of PRL on behavior, and its relation to immune system function, are discussed.