Behavioral effects of opioid subtypes compared with benzodiazepines in the staircase paradigm.
Opioid abuse is frequently associated with the abuse of benzodiazepines (BZ). Despite the fact that benzodiazepines and opioids act at totally separate receptor sites and through different biochemical and pharmacological mechanisms, they obviously interact with each other at some level. The present study was designed to investigate the behavioral effects of agents with activity on the opioid system and with the benzodiazepine receptor complex in the staircase paradigm. The benzodiazepine agonist lorazepam was used as a reference drug and showed a benzodiazepine effect: it reduced the rearing activity in mice in a dose-dependent manner, at doses that did not suppress climbing. Dissociation between the rearing and climbing behavior was not obtained with the administration of the opioid benzodiazepine, tifluadome, although tifluadome was antagonized by the BZ antagonist, flumazenil and not by naloxone, an opioid antagonist. An administration of opioids that act on the different subtype receptors morphine, U50 and SNC80, induced a dose dependent decrease in both the rearing and climbing activity, meaning no behavioral dissociation. Naloxone was found to have an antagonistic effect on morphine and U50-488H (micro and kappa subtype receptors, respectively), but no antagonistic effect on the delta subtype receptor agonist, SNC80. The administration of nalorphine to mice had no effect on both the rearing and climbing, in the staircase paradigm. When combining naloxone with the mentioned nalorphine, results showed the same effect, which was achieved with all the other opiates. This data, once again, supports the validity of the mouse staircase test for the identification of anxiolytic agents with a GABA(A) receptor complex-mediated activity, and for the ability to differentiate between diverse effects of the different opioids.
Milman
Anat
A
Department of Anatomy and Anthropology, Tel-Aviv University, Sackler Faculty of Medicine, Israel. anatmilman@gmail.com
Weizman
Ronit
R
Rigai
Tova
T
Rice
Kenner C
KC
Pick
Chaim G
CG
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects
D009294:Narcotics; D011963:Receptors, GABA-A; D011957:Receptors, Opioid; D001569:Benzodiazepines