The κ-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 κ-opioid receptor subtype antagonist nor-BNI (nor-Binaltorphimine), but not by the selective μ-opioid or the δ-opioid receptor subtype antagonists CTAP (d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2) 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 (κ-opioid receptor-like) pathway.