ArticlePsychopharmacology2019
The protein kinase Cβ-selective inhibitor, enzastaurin, attenuates amphetamine-stimulated locomotor activity and self-administration behaviors in rats.
Article in Psychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 4 citations in OpenAlex.
- PKC inhibition decreases amphetamine-maintained responding under a progressive-ratio schedule of reinforcement.Experimental and clinical psychopharmacology · 2021Article
- Novel Antimuscarinic Antidepressant-like Compounds with Reduced Effects on Cognition.The Journal of pharmacology and experimental therapeutics · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationalePathological amphetamine (AMPH) use is a serious public health concern with no pharmacological treatment options. Protein kinase Cβ (PKCβ) has been implicated in the mechanism of action of AMPH, such that inhibition of PKCβ attenuates AMPH-stimulated dopamine efflux in vivo. With this in mind, inhibition of PKCβ may be a viable therapeutic target for AMPH use disorder.
objectiveThe purpose of this study is to demonstrate that selective pharmacological inhibition of PKCβ alters AMPH-stimulated behaviors in rats.
methodsRats were administered intracerebroventricular (i.c.v.) injections of the PKCβ-selective inhibitor enzastaurin 0.5, 3, 6, or 18 h before evaluating AMPH-stimulated locomotion (0.32-3.2 mg/kg). Rats were trained to make responses for different doses of AMPH infusions or sucrose under a fixed ratio 5 schedule of reinforcement, and the effects of enzastaurin pretreatment 3 or 18 h prior to a self-administration session were determined. Also, the effect of enzastaurin on AMPH-stimulated PKC activity in the ventral striatum was evaluated.
resultsA large dose of enzastaurin (1 nmol) decreased AMPH-stimulated locomotor activity 0.5 h following enzastaurin administration. Small doses of enzastaurin (10-30 pmol) attenuated AMPH-stimulated locomotor activity and shifted the AMPH dose-effect curve to the right following an 18-h pretreatment. Rats pretreated with enzastaurin 18 h, but not 3, prior to a self-administration session showed a decrease in the number of responses for AMPH, shifted the ascending limb of the amphetamine dose effect curve, and produced no change in responses for sucrose. AMPH-stimulated PKC activity was decreased following a 0.5- or 18-h pretreatment, but not a 3-h pretreatment of enzastaurin.
conclusionsThese results demonstrate that inhibition of PKCβ will decrease AMPH-stimulated behaviors and neurobiological changes and suggest that PKCβ is potentially a viable target for AMPH use disorder.
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