Naloxone-blocked depriming effect of anxiolytic selank on apomorphine-induced behavioral manifestations of hyperfunction of dopamine system.
Peptide anxiolytic selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) applied intraperitoneally in doses of 0.01, 0.1, 1.0, and 10.0 mg/kg to mice reduces behavioral manifestations of dopaminergic system induced by apomorphine in the verticalization test. This effect was comparable to that of atypical antipsychotic olanzapine in near-therapeutic doses (0.1 and 1.0 mg/kg, intraperitoneally) and was blocked with nonselective opioid receptor antagonist naloxone (10 mg/kg, intraperitoneally). Radioreceptor assay showed that selank did not displace nonselective D2-dopamine receptor antagonist (3)H-spiperone (EC50>100 microM) and delta- and micro-opioid receptor ligand 3H-DADLE (EC50>40 microM) from specific binding sites on rat brain membranes. It is hypothesized that the revealed behavioral effect of selank is mediated by its modulating effect on the endogenous opioid system and specifically, by its effect on activity of enkephalin-degrading enzymes.
Meshavkin
V K
VK
Research Center of Mental Health, Russian Academy of Medical Sciences, Moscow. meshavkin@ rcmh.msk.ru
Kost
N V
NV
Sokolov
O Yu
OY
Zolotarev
Yu A
YA
Myasoedov
N F
NF
Zozulya
A A
AA
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D016308:Enkephalin, Leucine-2-Alanine / Q000378:metabolism; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology*; D000077152:Olanzapine; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
D014151:Anti-Anxiety Agents; D009842:Oligopeptides; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; D001569:Benzodiazepines; D009270:Naloxone; D013134:Spiperone; D016308:Enkephalin, Leucine-2-Alanine; D001058:Apomorphine; D000077152:Olanzapine; C100827:TP 7; D004298:Dopamine