Blockade of the orexin 1-receptors and ‘cocaine- and amphetamine-regulated transcript’ in the nucleus accumbens shell alters impulse control in rats

Abstract

Impulsivity is a multifaceted construct and alterations in impulsiveness are often associated with psychiatric diseases, including drug addiction and binge eating disorder. Impulse control involves several brain regions. The present study assessed the role of the orexigenic, appetite stimulating neuropeptide orexin (OX) and the anorexigenic, appetite reducing neuropeptide cocaine- and amphetamine-regulated transcript (CART) within the nucleus accumbens shell (NAcSh) in impulse control in rats. The animals were ranked for their trait impulsivity based on a screening in the 5-choice serial reaction time task (5-CSRTT). The rats’ performances were analysed after bilateral infusions of the OX 1-receptor antagonist SB-334867 (SB) and CART-antibodies (CART-ABs) into the NAcSh. After SB infusions, there was no change in premature responses observed on average. Further analysis revealed a negative linear correlation between the effect of intra-NAcSh SB infusions on premature responses and trait impulsivity. The effect of SB ranged from an increase, no change to a decrease in premature responses in the individual animals with increasing trait impulsivity. Infusions of CART-ABs led to consistently enhanced impulse control with fewer irrelevant actions, independent of trait impulsivity. These data suggest that both OX, especially OX A, and CART in the NAcSh, can be considered endogenous regulators of impulsive action, dependent on underlying impulsivity in the case of OX and independent from trait impulsivity in the case of CART.