Haloperidol-induced hyperactivity in neonatal rats: effect of lithium and stimulants

The effect of chronic subcutaneous administration of haloperidol directly into neonatal rats was investigated as a possible model for the hyperkinetic syndrome in human children in terms of its onset, duration and offset of hyperactivity. In addition, the ability of chronically-administered lithium in the diet of nursing mothers to attenuate the haloperidol-induced hyperactivity was investigated. Experiments with acute administration of the clinically-effective stimulants, amphetamine and methylphenidate, to the pups were also conducted to determine the adequacy of this behavioral model vis-a-vis the human condition. The results indicate that, although chronic haloperidol (2.5 mg/kg) produced hyperactivity relative to controls on the 25th day of life, this hyperactive behavior does not return to control levels at 30 days of age. Moreover, neither the stimulants nor lithium attenuates this hyperactivity and, indeed, lithium, by itself, produces increased activity. Thus, chronic haloperidol administered directly into neonatal rat pups produces hyperactivity possibly by the production of dopaminergic supersensitivity, yet this effect does not model the temporal course seen in hyperkinetic humans. In addition, the administration of drugs that are clinically-useful in treating childhood hyperactivity were unable to decrease the hyperactivity produced by haloperidol in neonatal rats. Taken together, these observations cast doubt upon the usefulness of this animal model to mimic the human condition.