Gregory W. Stagliano

κ-Opioid withdrawal in Planaria

Abstract Many drug-abusers engage in poly-drug abuse, but there has been relatively little quantification of withdrawal from poly-drug use. Planarians are an advantageous model for these studies due to mammalian-relevant neurotransmitter systems (e.g. dopamine, opioid, and 5-HT). We recently developed a metric that quantified an acute cocaine withdrawal phenomenon in planarians. However, despite much indirect evidence, we lacked direct evidence of a receptor- or carrier-mediated effect. We now report dose-related, naloxone- and nor-binaltorphine-sensitive acute abstinence-induced withdrawal and naloxone-precipitated withdrawal from the κ-opioid agonist U-50,488H ( trans -(±)-3,4-dichloro- N -methyl- N -(2-[1-pyrrolidinyl]cyclohexyl)-benzeneacetamide). The less active enantiomer [ 1R , 2R ]U-50,488 produced significantly less withdrawal and U-50,488H withdrawal was not due to pH or osmolarity. These data provide pharmacologic evidence of a κ-opioid receptor-mediated withdrawal phenomenon and neuroadaptation to a pharmacologic stimulus (adaptations in transduction mechanisms) in this model.

Cocaine and κ-opioid withdrawal in Planaria blocked by d-, but not l-, glucose

Abstract Planarians (Dugesia dorotocephala) that were exposed for 1 h to cocaine (80 μM) or to the κ-selective opioid receptor agonist U-50,488H (1 μM) 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 d -glucose (1 μM) or to 2-deoxy- d -glucose (2-DG, 1 μM), but not to l -glucose (1 μM), significantly attenuated (P d -glucose and 2-deoxy- d -glucose compete with a common cocaine and κ-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.