Nociceptin attenuates methamphetamine abstinence-induced withdrawal-like behavior in planarians.
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 microM) were tested in drug-free water. The withdrawal-like behavior was abolished when methamphetamine (10 microM)-exposed planarians were placed into water containing nociceptin (10 microM) or when planarians co-exposed to methamphetamine (10 microM) and nociceptin (10 microM) were placed into drug-free water. The effects of nociceptin were abolished in the presence of a nociceptin receptor antagonist, JTC-801 (1 microM). Planarians did not display a change in locomotor behavior during exposure to nociceptin (10 microM) or JTC-801 (1 microM) by themselves. These results (1) reveal a functional interaction between nociceptin and methamphetamine in planarians and (2) provide evidence that nociceptin blocks methamphetamine-induced withdrawal-like behavior in planarians through a JTC-801-sensitive mechanism.
Rawls
Scott M
SM
Department of Pharmaceutical Sciences, Temple University School of Pharmacy and Center for Substance Abuse Research, Philadelphia, PA 19140, USA. scott.rawls@temple.edu
Baron
Steven
S
Ding
Zhe
Z
Roth
Christopher
C
Zaveri
Nurulain
N
Raffa
Robert B
RB
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D000697:Central Nervous System Stimulants; D066298:In Vitro Techniques; D008694:Methamphetamine; D009043:Motor Activity / Q000187:drug effects; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010932:Planarians / Q000502:physiology*; D011957:Receptors, Opioid; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000634:Aminoquinolines; D001549:Benzamides; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C433236:N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide