Behavioral effects of systemically administered mu and kappa opioid agonists in the squirrel monkey: peptides versus alkaloids.
This study compared the effects of receptor-selective peptide and nonpeptide opioid agonists administered intramuscularly to squirrel monkeys responding under a fixed-interval 3-min schedule of stimulus termination. The mu opioid receptor agonist morphine (0.1-3.0 mg/kg) increased response rate at low doses and decreased it and quarter-life at higher doses. [D-Ala2,N-Me-Phe4,Gly-ol]Enkephalin (DAMGO; 0.3-3.0 mg/kg) reduced quarter-life at the highest dose. The kappa dose. The kappa opioid receptor agonist U50,488H (0.1-1.0 mg/kg) elevated response rate transiently and dose-dependently decreased quarter-life. Dynorphin A(1-13) (0.3-10 mg/kg), a purported endogenous ligand of the kappa opioid receptor, decreased response rate slightly but significantly at 3.0 mg/kg and had no effect on quarter-life. Thus, the behavior of squirrel monkeys was affected by systemically administered peptide as well as by nonpeptide opioid drugs. The two alkaloids were much more effective than the two peptides, presumably because of greater ability to penetrate the blood-brain barrier. Quarter-life was often a more sensitive measure of drug effects than was response rate.
Jones
D N
DN
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322-3090.
Holtzman
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SG
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000470:Alkaloids / Q000493:pharmacokinetics / Q000494:pharmacology*; D000700:Analgesics / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004399:Dynorphins / Q000493:pharmacokinetics / Q000494:pharmacology; D004723:Endorphins / Q000493:pharmacokinetics / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000493:pharmacokinetics / Q000494:pharmacology; D007273:Injections, Intramuscular; D008297:Male; D009020:Morphine / Q000493:pharmacokinetics / Q000494:pharmacology; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology; D011759:Pyrrolidines / Q000493:pharmacokinetics / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D012055:Reinforcement Schedule; D012453:Saimiri
D000470:Alkaloids; D000700:Analgesics; D004723:Endorphins; D004745:Enkephalins; D010446:Peptide Fragments; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine