Chemokine receptor expression in cultured glia and rat experimental allergic encephalomyelitis.

Chemokines are a group of pro-inflammatory peptides that mediate leukocyte migration and activation. Several members of the chemokine family have been shown to be synthesized by cells of the central nervous system (CNS). To begin to address the role of chemokine receptors in CNS physiology, we identified, by molecular cloning techniques, the rat orthologs of the chemokine receptors, CCR2, CCR3, CCR5, and CXCR4. CCR2 and CCR5 expression was detected in rat spleen, lung, kidney, thymus and macrophages; CCR5 mRNA was also detected in rat brain. Primary cultures of rat microglia expressed CCR5 mRNA that was regulated by IFN-gamma, while both cultured astrocytes and microglia were found to contain mRNA for CXCR4 and CX3CR1. Induction of experimental allergic encephalomyelitis (EAE) in the rat was accompanied by increased levels of CCR2, CCR5, CXCR4, and CX3CR1 mRNAs in the lumbar spinal cords of animals displaying clinical signs of the disease. These data identify the rat orthologs of chemokine receptors and demonstrate that brain, spinal cord, and cultured glial cells express chemokine receptors that can be regulated both in vitro and in vivo.

Genetic differences in the establishment of ethanol as a reinforcer.

Ethanol, self-administered orally, has been shown to serve as an effective reinforcer in several species. Self-administration studies have also illustrated that ethanol-drinking behavior can be conceptualized as a specific type of operant behavior. The use of inbred and selectively bred animals in other areas of alcohol research has provided valuable information about the contribution of genetic factors to ethanol-related behaviors. Our research was designed to study genetic differences in oral self-administration in the ALKO AA (Alcohol Accepting) and ANA (Alcohol Non-Accepting) rat lines, selected for ethanol preference. Thus, we applied a behavior genetic analysis to aid in determining the contribution of genetic factors to behavior, specifically drug-seeking behavior. The results of our experiments indicate that genetic differences are important factors contributing to the establishment of a drug as a reinforcer. At least in the case of ethanol, the drug did not act as a reinforcer in non-preferring animals. Conversely, in preferring animals, ethanol was readily established as a reinforcer.