Chronic GBR 12909 administration differentially alters prodynorphin gene expression compared to cocaine

The effect of the selective dopamine uptake inhibitor 1-[2-[bis(4-flourophe nyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride (GBR 12909) was examined on prodynorphin gene expression. GBR 12909 or vehicle was con tinuously infused for 7 days via osmotic minipump, or injected daily into m ale rats. Both continuous infusions and daily injections of GBR 12909 produ ced significant decreases in prodynorphin expression in the hypothalamus (3 7% and 31% decreases, respectively). There were no significant changes in t he caudate putamen, hippocampus or nucleus accumbens. One injection of GBR 12909 had no effects on prodynorphin expression in any of the brain regions studied, suggesting that the effect in the hypothalamus is not an acute ef fect. As previously reported for other treatment regimens, continuous infus ion of cocaine produced a 35% significant decrease in the hypothalamus, con sistent with the effects of GBR 12909. In contrast to GBR 12909, however, c ocaine also produced a significant increase in prodynorphin expression in t he caudate putamen. Thus, chronic inhibition of dopamine uptake can regulat e prodynorphin expression in the hypothalamus. In contrast, the increase in the caudate putamen following cocaine administration may not be related to the inhibition of dopamine uptake, since it was not produced by a selectiv e dopamine uptake inhibitor. These findings suggest that regulation of prod ynorphin gene expression by cocaine in the caudate putamen may be mediated by the inhibition of norepinephrine or serotonin uptake, by a combination o f effects on two or three monoamine transporters, or by a mechanism unrelat ed to transporter inhibition. (C) 2001 published by Elsevier Science B.V.