Narp is an immediate early gene product that acts extracellularly to cluster AMPA receptors at excitatory synapses. The present study tested the hypothesis that drugs of abuse alter Narp expression and thereby influence AMPA receptor transmission in addiction-related circuits. Immunohistochemical studies demonstrated the existence of Narp-positive cells in hippocampus, prefrontal cortex (PFC) and nucleus accumbens (NAc), with lower levels of staining in the ventral tegmental area (VTA). To study the effects of psychomotor stimulants, Narp levels were quantified by Western blotting and normalized to actin. There were no differences in Narp levels in any brain region between rats treated with repeated saline injections, a single amphetamine injection (5 mg/kg), repeated amphetamine injections (5 mg/kg x 5 days), or repeated cocaine injections (20 mg/kg twice daily x 7 days). We also examined the possible role of Narp in individual differences in responding to a novel environment, a predictor of behavioural responses to psychomotor stimulant drugs including the propensity to acquire drug self-administration. Narp levels in the PFC, but not other regions, were significantly correlated with locomotor activity in a novel environment. These findings suggest that differential Narp expression in the PFC may be involved in determining individual vulnerability to drugs of abuse, perhaps by influencing the activity of its excitatory projections.