PKC inhibition decreases amphetamine-maintained responding under a progressive-ratio schedule of reinforcement
| Autor: | Ryan C Mac, Emily M. Jutkiewicz, Rachel Altshuler, Margaret E. Gnegy |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Reinforcement Schedule Self Administration Pharmacology Article Rats Sprague-Dawley chemistry.chemical_compound Enzastaurin medicine Animals Pharmacology (medical) Reinforcement Amphetamine Protein kinase C Dose-Response Relationship Drug Kinase Chemistry Rats Psychiatry and Mental health Mechanism of action Central Nervous System Stimulants Progressive ratio medicine.symptom Reinforcement Psychology Extracellular dopamine medicine.drug |
| Zdroj: | Exp Clin Psychopharmacol |
| ISSN: | 1936-2293 1064-1297 |
| Popis: | 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 PKCβ-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). |
| Databáze: | OpenAIRE |
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