The cytokine, interleukin-1β (IL1β) is a sleep regulatory substance whose expression is enhanced in response to neuronal stimulation. In this study, IL1β mRNA and immunoreactivity (IR) are evaluated after acute cocaine. First, IL1β mRNA levels were measured at the start or end of the light period after saline or acute exposure to a low dose of cocaine (5 mg/kg, intraperitoneal (ip)). IL1β mRNA levels after an acute exposure to cocaine (5 mg/kg, ip) at dark onset were significantly higher than those obtained from rats sacrificed after an acute exposure to saline in the piriform and somatosensory cortex, and nucleus accumbens. Acute exposure of cocaine at 5 mg/kg at dark onset also increased the number of IL1β-immunoreactive astrocytes in layer I-V of the prefrontal cortex, somatosensory cortex and nucleus accumbens. These data suggest that IL1β mRNA and protein levels in some of the dopaminergically innervated brain regions are responsive to cocaine.