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PKC inhibition decreases amphetamine-maintained responding under a progressive-ratio schedule of reinforcement. 2021

Rachel D Altshuler, and Ryan C Mac, and Margaret E Gnegy, and Emily M Jutkiewicz
Department of Pharmacology, University of Michigan.

Protein kinase C (PKC) is important for the mechanism of action of amphetamine (AMPH). Inhibiting PKC blocks AMPH-stimulated increases in extracellular dopamine levels and AMPH-stimulated locomotor activity. This study examined the effects of PKC inhibition on the reinforcing properties of AMPH. Male Sprague-Dawley rats were trained to respond for infusions of 0.032 mg/kg/infusion AMPH or for sucrose pellets under a progressive-ratio (PR) schedule of reinforcement. Number of infusions earned, breakpoints, and session duration were recorded over consecutive sessions. Once AMPH-maintained responding stabilized, rats were treated with 0, 10, or 30 pmol of enzastaurin, a PKCĪ²-selective inhibitor, or 6 mg/kg 6c, a brain-permeable PKC inhibitor, 18 hr prior to a self-administration session. Pretreatment with 30 pmol enzastaurin or 6 mg/kg 6c decreased the number of AMPH infusions earned and breakpoints without altering sucrose-maintained behaviors. These data suggest that PKC inhibition decreases motivation for AMPH and, therefore, is worth pursuing as a potential treatment for AMPH-use disorder. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

UI MeSH Term Description Entries
D008297 Male Males
D012054 Reinforcement, Psychology The strengthening of a conditioned response. Negative Reinforcement,Positive Reinforcement,Psychological Reinforcement,Reinforcement (Psychology),Negative Reinforcements,Positive Reinforcements,Psychological Reinforcements,Psychology Reinforcement,Psychology Reinforcements,Reinforcement, Negative,Reinforcement, Positive,Reinforcement, Psychological,Reinforcements (Psychology),Reinforcements, Negative,Reinforcements, Positive,Reinforcements, Psychological,Reinforcements, Psychology
D012055 Reinforcement Schedule A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent. Reinforcement Schedules,Schedule, Reinforcement,Schedules, Reinforcement
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
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
D012646 Self Administration Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. Administration, Self,Administrations, Self,Self Administrations
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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