Opioid Receptor Agonists Selective for μ and κ Receptors Attenuate Methamphetamine-Induced Behavioral Sensitization in the Mouse

• Published in: Biological & pharmaceutical bulletin Vol. 19; no. 3; pp. 369 - 374
• Main Authors: TOYOSHI, Tohru, UKAI, Makoto, KAMEYAMA, Tsutomu
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1996; Maruzen
• Subjects: [D-Ala2, N-MePhe4, Gly-ol] enkephalin; Analgesics - administration & dosage; Analgesics - pharmacology; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacology; Animals; Behavior, Animal - drug effects; behavioral sensitization; Biological and medical sciences; Central Nervous System Stimulants - antagonists & inhibitors; Central Nervous System Stimulants - pharmacology; Drug Tolerance; dynorphin A-(1-13); Dynorphins - administration & dosage; Dynorphins - pharmacology; Enkephalin, Ala-MePhe-Gly; Enkephalins - administration & dosage; Enkephalins - pharmacology; Grooming - drug effects; Injections, Intraventricular; Male; Medical sciences; methamphetamine; Methamphetamine - antagonists & inhibitors; Methamphetamine - pharmacology; Mice; Mice, Inbred Strains; Motor Activity - drug effects; mouse; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Receptors, Opioid, kappa - agonists; Receptors, Opioid, mu - agonists; reverse tolerance; Stereotyped Behavior - drug effects; Time Factors; Amphetamine derivatives; Vertebrata; Agonist; Mammalia; Mouse; Animal; Rodentia; Behavior; Opiate receptor μ; Opiate receptor κ
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.19.369

The effects of intracerebroventricular (i.c.v.) injection of the μ-selective opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol] enkephalin (DAMGO) and the κ-selective opioid receptor agonist dynorphin A-(1-13) on the development of methamphetamine-induced behavioral sensitization in the mouse were determined using multidimensional behavioral analyses based upon a capacitance system. Methamphetamine (2mg/kg, s.c.) was administered to mice on 6 occasions at 3-or 4-d intervals. The methamphetamine-induced increase in linear locomotion and circling was markedly augmented by repeated administrations (3 or more times) of the drug, showing behavioral sensitization. Although repeated administrations of DAMGO (0.003 and 0.01μg, i.c.v.) or dynorphin A-(1-13) (3 and 12.5μg, i.c.v.) alone did not produce any significant effects on behavior, repeated administrations of DAMGO (0.003 and 0.01μg, i.c.v.) and dynorphin A-(1-13) (3 and 12.5μg, i.c.v.) attenuated the behavioral sensitization induced by methamphetamine (2mg/kg, s.c.). The attenuating effects of DAMGO (0.003 and 0.01μg, i.c.v.) and dynorphin A-(1-13) (3 and 12.5μg, i.c.v.) were fully reversed by withdrawal of these drugs for 3 weeks. Additionally, a single administration of DAMGO (0.003 and 0.01μg, i.c.v.) or dynorphin A-(1-13) (3 and 12.5μg, i.c.v.) alone did not produce any significant effects on behavior ; DAMGO (0.003 and 0.01μg, i.c.v.) and dynorphin A-(1-13) (3 and 12.5μg, i.c.v.) only attenuated the behavioral sensitization which had previously been developed by methamphetamine (2 mg/kg, s.c.). These results suggest that opioid receptor agonists selective for μ and κ receptors play an inhibitory role in the development of methamphetamine-induced behavioral sensitization.