Nociceptin Attenuates Methamphetamine Abstinence-Induced Withdrawal-Like Behavior in Planarians

Abstract

Planarians display a concentration-related reduction in locomotor activity when amphetamine, cocaine, cannabinoid, or benzodiazepine exposure is abruptly discontinued. In the present study, we tested the hypothesis that abrupt discontinuation of methamphetamine would also cause withdrawal-like behavior in planarians and that the withdrawal-like behavior would be prevented by nociceptin, which has been shown to modulate the effects of methamphetamine in mammals. We observed a concentration-related reduction of locomotor behavior when planarians exposed to methamphetamine (0.1–100 μM) were tested in drug-free water. The withdrawal-like behavior was abolished when methamphetamine (10 μM)-exposed planarians were placed into water containing nociceptin (10 μM) or when planarians co-exposed to methamphetamine (10 μM) and nociceptin (10 μM) were placed into drug-free water. The effects of nociceptin were abolished in the presence of a nociceptin receptor antagonist, JTC-801 (1 μM). Planarians did not display a change in locomotor behavior during exposure to nociceptin (10 μM) or JTC-801 (1 μM) by themselves. These results reveal a functional interaction between nociceptin and methamphetamine in planarians and provide evidence that nociceptin blocks methamphetamine-induced withdrawal-like behavior in planarians through a JTC-801-sensitive mechanism.