Open AccessPKC inhibition decreases amphetamine-maintained responding under a progressive-ratio schedule of reinforcement.
Author(s) -
Rachel Altshuler,
Ryan C Mac,
Margaret E. Gnegy,
Emily M. Jutkiewicz
Publication year - 2021
Publication title -
experimental and clinical psychopharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.066
H-Index - 92
eISSN - 1936-2293
pISSN - 1064-1297
DOI - 10.1037/pha0000425
Subject(s) - reinforcement , amphetamine , dextroamphetamine , pharmacology , psychology , schedule , neuroscience , anesthesia , medicine , dopamine , computer science , social psychology , operating system
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).