Impulsivity in NrCAM KO Mice Is Reduced by NMDAR Antagonist MK-801 but Not by AMPAR Antagonist CNQX

The neuronal cell adhesion molecule NrCAM is widely expressed in the nervous system across the lifespan and has important physiological functions in the development of neuronal circuits through axonal growth and guidance and formation and maintenance of synapses in the cortex. NrCAM gene polymorphisms are associated with vulnerability to neuropsychiatric disorders such as schizophrenia, as well as vulnerability to substance use disorders. We investigated the effects of acute and chronic stress and the effects of systemic administration of AMPAR antagonist CNQX and NMDAR antagonist MK-801 on delay discounting in male NrCAM knockout (KO) mice and their wild-type littermate controls (WT). Under the no-stress condition, no discounting differences were found. Acute stress increased discounting and impulsivity in WTs but not in NrCAM KO mice. Chronic stress increased discounting and impulsivity in both genotypes. CNQX increased impulsive choice in WT controls but not in NrCAM KOs; impulsive choice decreased in both genotypes after MK-801 administration. Relative to WTs, NrCAM KOs had more neuronal activation in the prelimbic and orbitofrontal cortices. In NrCAM KO mice, a low dose of MK-801 decreased neuronal activation in the ventral orbitofrontal cortex and increased activation in the accumbens shell and core. These results indicate differential effects of genotype, stress, and response to glutamatergic drugs and support a role for NrCAM in stress-induced behavioral alterations relevant to addiction and psychiatric disorders.