The kappa-opioid receptor antagonist nor-BNI inhibits cocaine and amphetamine, but not cannabinoid (WIN 52212-2), abstinence-induced withdrawal in planarians: an instance of 'pharmacologic congruence'.
The broad applicability of receptor theory to diverse species, from invertebrates to mammals, provides evidence for the evolution in complexity of pharmacologic receptor diversification and of receptor-effector signal transduction mechanisms. However, pre-mammalian species have less receptor subtype differentiation, and thus, might share signal transduction pathways to a greater extent than do mammals, a phenomenon that we term 'pharmacologic congruence'. We have demonstrated previously that the lowest species considered to have a centralized nervous system, planarians, display both abstinence-induced and antagonist-precipitated withdrawal signs, indicative of the development of physical dependence. We report here: (1) amphetamine abstinence-induced withdrawal, and (2) the attenuation of cocaine and amphetamine, but not cannabinoid agonist (WIN 52212-2), abstinence-induced withdrawal by the opioid receptor antagonist naloxone and by the selective kappa-opioid receptor subtype antagonist nor-BNI (nor-Binaltorphimine), but not by the selective mu-opioid or the delta-opioid receptor subtype antagonists CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)) and naltrindole. These results provide evidence that the withdrawal from cocaine and amphetamine, but not cannabinoids, in planarians is mediated through a common nor-BNI-sensitive (kappa-opioid receptor-like) pathway.
Raffa
Robert B
RB
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA. robert.raffa@temple.edu
Stagliano
Gregory W
GW
Ross
Geoffrey
G
Powell
Jenay A
JA
Phillips
Austin G
AG
Ding
Zhe
Z
Rawls
Scott M
SM
D000661:Amphetamine / Q000009:adverse effects*; D000700:Analgesics / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000009:adverse effects; D003042:Cocaine / Q000009:adverse effects*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D004347:Drug Interactions; D009025:Morpholines / Q000009:adverse effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009281:Naphthalenes / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010932:Planarians; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D013997:Time Factors
D000700:Analgesics; D048588:Benzoxazines; D018765:Dopamine Uptake Inhibitors; D009025:Morpholines; D009281:Naphthalenes; D009292:Narcotic Antagonists; C051844:norbinaltorphimine; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009271:Naltrexone; D000661:Amphetamine; D003042:Cocaine