Increased locomotor response to amphetamine induced by the repeated administration of the selective kappa-opioid receptor agonist U-69593. 2007

José Antonio Fuentealba, and Katia Gysling, and María Estela Andrés
Department of Pharmacy, Faculty of Chemistry, Pontificia Universidad Catolica de Chile, Alameda, Santiago, Chile.

Acute administration of kappa opioid receptor (KOR) agonists decreases both dopamine (DA) extracellular levels in the nucleus accumbens (NAc) and locomotor activity. Opposing to its acute effects, recent studies show that chronic administration of KOR agonists potentiates both stimulated DA release and induced locomotor activity. Since KOR agonists have been considered as potential treatment for stimulant dependence, the effects of their repeated administration on psychostimulant actions are of major concern. The present study was undertaken to investigate the in vivo effect of repeated administration of the KOR agonist U-69593 on DA extracellular levels in the NAc and on the locomotor activity challenged with amphetamine. Rats were injected once daily with the selective KOR agonist U-69593 or vehicle for four consecutive days. One-day after the last U-69593 injection, microdialysis studies assessing extracellular DA levels in the NAc and locomotor activity challenged with amphetamine were conducted. Microdialysis studies revealed that preexposure to U-69593 had no effect on basal DA levels but significantly augmented amphetamine-induced DA extracellular levels. Accordingly, amphetamine-induced locomotor activity was also significantly potentiated in U-69593 preexposed rats. These results suggest that long-term effect of KOR activation results in facilitation of amphetamine-induced DA extracellular levels in the NAc accompanied by sensitization of amphetamine-induced increase in locomotor activity.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D000661 Amphetamine A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE. Desoxynorephedrin,Levoamphetamine,Phenopromin,l-Amphetamine,Amfetamine,Amphetamine Sulfate,Amphetamine Sulfate (2:1),Centramina,Fenamine,Mydrial,Phenamine,Thyramine,levo-Amphetamine,Sulfate, Amphetamine,l Amphetamine,levo Amphetamine
D000697 Central Nervous System Stimulants A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. Analeptic,Analeptic Agent,Analeptic Drug,Analeptics,CNS Stimulant,CNS Stimulants,Central Nervous System Stimulant,Central Stimulant,Analeptic Agents,Analeptic Drugs,Central Stimulants,Agent, Analeptic,Agents, Analeptic,Drug, Analeptic,Drugs, Analeptic,Stimulant, CNS,Stimulant, Central,Stimulants, CNS,Stimulants, Central
D000700 Analgesics Compounds capable of relieving pain without the loss of CONSCIOUSNESS. Analgesic,Anodynes,Antinociceptive Agents,Analgesic Agents,Analgesic Drugs,Agents, Analgesic,Agents, Antinociceptive,Drugs, Analgesic
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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