Psychostimulants differentially alter performance on the rodent psychomotor vigilance test following radiation exposure

Abstract

To investigate radiation‐induced cognitive deficits, the present report describes performance data obtained with the rPVT (rat Psychomotor Vigilance Test), an animal analog of the human PVT test currently employed in a variety of operational settings. The human PVT was developed as a highly sensitive and standardized assay capable of quantifying temporally dynamic changes in sustained attention, and requires responding to a light stimulus as soon as it appears. In the current study, rats were trained to perform the rPVT to baseline performance levels (≥75% correct and ≤25% premature responses) and were then irradiated with head‐only protons (150 MeV/n) at 25 or 100 cGy or sham‐irradiation. Following radiation exposure, rats were returned to Hopkins and continued daily rPVT assessments. At approximately 6 months post‐radiation exposure, rats were then characterized as radiation sensitive—i.e., those rats displaying radiation‐induced rPVT deficits, or radiation insensitive—i.e., irradiated rats performing the rPVT at sham‐irradiated control levels. Several different drugs were then assessed as countermeasures for these deficits in radiation sensitive rats, and were also assessed in radiation insensitive rats to determine if any performance disruptions would occur. d‐Amphetamine dose‐dependently improved performance in radiation sensitive rats, whereas it impaired rPVT performance in radiation insensitive rats at the two highest doses tested. Amphetamine's effects were decreased by the D1 antagonist, SCH 39166, but not the D2 antagonist, L‐741, 626. Atomoxetine and methylphenidate were also tested, but did not produce these differential effects. This data further supports the role of the dopamine neurotransmitter system in mediating individual differences in radiation‐induced deficits in neurobehavioral performance as assessed by the rPVT.Support or Funding InformationSupported by the NSBRI through NASA cooperative agreement NCC 9‐58, grants NBPF01604, NBPF02802, NBPF04201, and EO00010, and NASA NNX15AC71G