Mu Opioid Receptor Agonist DAMGO Produces Place Conditioning, Abstinence-induced Withdrawal, and Naltrexone-Dependent Locomotor Activation in Planarians

Unlike the behavioral effects planarians display when exposed to cocaine, amphetamines, cathinones, ethanol and sucrose, effects of opioid receptor agonists, especially mu opioid receptor agonists, are poorly defined in these flatworms. Here, we tested the hypothesis that planarians exposed to a selective mu opioid receptor agonist, DAMGO (0.1, 1, 10 µM), would display a triad of opioid-like effects (place conditioning, abstinence-induced withdrawal, and motility changes). DAMGO was selected versus morphine because of its greater mu opioid receptor selectivity. In place conditioning and abstinence experiments, the planarian light/dark test (PLDT) was utilized (i.e., planarians are placed into a petri dish containing water that is split into light and dark compartments and time spent in the compartments is determined). Planarians conditioned with DAMGO (1 µM) spent more time on the drug-paired side compared to water controls. In abstinence experiments, planarians exposed to DAMGO for 30 min were removed and then placed into water, where light avoidance (e.g. defensive responding) and depressant-like effects (i.e., decreased motility) were quantified. Compared to water controls, DAMGO-withdrawn planarians spent less time in the light (10 µM) and displayed decreased motility (1, 10 µM). Acute DAMGO exposure (1 µM) produced hypermotility that was antagonized by naltrexone (1, 10, 100 µM). In contrast, acute exposure to the kappa opioid receptor agonist U50,488H (0.1, 1, 10 µM) resulted in decreased motility. Our results show that a mu opioid agonist produces mammalian-like behavioral responses in planarians that may be related to addiction and suggest opioid-like behavioral effects are conserved in invertebrates.