Cocaine and kappa-opioid withdrawal in Planaria blocked by D-, but not L-, glucose.

Planarians (Dugesia dorotocephala) that were exposed for 1 h to cocaine (80 microM) or to the kappa-selective opioid receptor agonist U-50,488H (1 microM) displayed an abstinence-induced withdrawal syndrome, indicative of the development of physical dependence, when they were tested in cocaine- (or U-50,488H-) free water, but not when they were tested in cocaine- (or U-50,488H-) containing water. The withdrawal was manifested as a significant (P<0.05) decrease in the rate of planarian spontaneous locomotor activity over a 5-min observation period, using a recently designed metric. Co-exposure of the planarians to D-glucose (1 microM) or to 2-deoxy-D-glucose (2-DG, 1 microM), but not to L-glucose (1 microM), significantly attenuated (P<0.05) the development of physical dependence, shown by an attenuated withdrawal syndrome, from cocaine and U-50,488H. These results suggest that either D-glucose and 2-deoxy-D-glucose compete with a common cocaine and kappa-opioid transport mechanism or that the development of physical dependence (or the inhibition of abstinence-induced withdrawal) in planarians requires energy supplied from glucose metabolism.