Attenuation of pharmacologically-induced attentional impairment by methylphenidate in rats

Methylphenidate is widely used as a treatment option for attention deficit hyperactivity disorder. In animal models of attentional impairment, it is an important validation to determine whether this clinically effective treatment attenuates deficits. The purpose of the current study was to determine whether methylphenidate can diminish attentional impairment induced by three pharmacological agents with different mechanisms of action: scopolamine, mecamylamine, and dizocilpine. Female rats were trained on an operant visual signal detection task. Ten min before the test, the rats were injected subcutaneously with methylphenidate (0, 0.1, 0.3 mg/kg), scopolamine (0, 0.005, 0.01 mg/kg), mecamylamine (0, 2, 4 mg/kg), dizocilpine (0, 0.025, 0.05 mg/kg) or combinations of methylphenidate with these drugs. In each of the experiments, all rats received every treatment in a repeated measures counterbalanced order. Correction rejection accuracy was impaired by all three of the antagonists and these effects were attenuated by methylphenidate. Both scopolamine at 0.01 and dizocilpine at 0.05 mg/kg significantly impaired percent correct rejection choice accuracy, an effect that was ameliorated by methylphenidate. Mecamylamine (4 mg/kg) impaired attentional performance by reducing percent hit and percent correct rejection. Co-administration of methylphenidate failed to significantly affect the mecamylamine-induced attentional impairment. Methylphenidate alone at 0.3 mg/kg significantly improved percent hit choice accuracy only in low-performing rats in one experiment, an effect which was reversed by scopolamine. These data show that methylphenidate effectively reverses the attentional impairment caused by scopolamine and dizocilpine. These findings further validate the operant visual signal detection task for assessing attentional impairments and their reversal.