Pain-induced Impulsivity and Its Reduction with Amphetamine in Rats

Abstract

Pain is known to produce various cognitive changes, including increased impulsivity in humans and animals. Increases in impulsivity may facilitate the development of psychiatric conditions such as substance use disorders and anxiety disorders. We have previously shown that Complete Freund's Adjuvant (CFA)-induced pain increases impulsivity in rats. Amphetamine is a central nervous system stimulant used to treat impulse control disorders by increasing monoaminergic activity in the brain. This study aimed to determine whether amphetamine can reduce pain-induced impulsivity and nociception in rats. Pain-induced impulsivity was assessed using a delay discounting task in male and female rats. Initial baseline tests were employed to screen for trait impulsivity and identify low and high impulsive rats. After intraplantar CFA injection, daily saline or amphetamine (0.25, 0.5, or 1.0 mg/kg) was given, and impulsivity was assessed over sixteen days. Animals were also examined for potential antinociceptive effects of amphetamine on CFA-induced tactile allodynia. CFA treatment increased impulsivity in high impulsive rats more than low impulsive rats. Repeated amphetamine administration blocked pain-induced impulsivity in a dose manner. Amphetamine began to block impulsivity after six daily injections. CFA-induced mechanical allodynia was not reduced by amphetamine. Our results show amphetamine's propensity to prevent pain-induced impulsivity, independent of treating nociception. While pain-induced cognitive deficits may proliferate from pain states, their treatment and continued expression may be independent of pain sensation.