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.
Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Sumiyo
S
Umeda
Gregory W
GW
Stagliano
Robert B
RB
Raffa
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000222:Adaptation, Physiological; D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism / Q000503:physiopathology; D002236:Carbohydrate Conformation; D003042:Cocaine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005947:Glucose / Q000737:chemistry* / Q000378:metabolism*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D010932:Planarians / Q000187:drug effects* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology
D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D003042:Cocaine; D005947:Glucose