CXCR4 inhibition with AMD3100 attenuates amphetamine induced locomotor activity in adolescent Long Evans male rats
Autor: | S. Tiffany Donaldson, Antonio Alves, Corey Calhoun, Victoria Woytowicz, Briana Mason, Latifa Pina, Roshninder Kanda, Curtis Dunn |
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Rok vydání: | 2020 |
Předmět: |
Male
Benzylamines Physiology Social Sciences Striatum Cyclams Chemokine receptor Medicine and Health Sciences Psychology CXC chemokine receptors Sensitization Mammals Multidisciplinary CXCR4 antagonist Animal Behavior Chemotaxis Dopaminergic Drugs Eukaryota Brain Long-term potentiation Animal Models Cell Motility medicine.anatomical_structure Experimental Organism Systems Vertebrates Medicine Sensory Perception Anatomy Chemokines Locomotion medicine.drug Research Article medicine.medical_specialty Receptors CXCR4 Anti-HIV Agents Science Research and Analysis Methods Rodents Model Organisms Internal medicine medicine Animals Rats Long-Evans Amphetamine Pharmacology Behavior business.industry Biological Locomotion Cognitive Psychology Organisms Biology and Life Sciences Cell Biology Rats Neostriatum Endocrinology Gene Expression Regulation Amniotes Animal Studies Cognitive Science Central Nervous System Stimulants Perception business Zoology Psychostimulants Neuroscience |
Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 3, p e0247707 (2021) |
ISSN: | 1932-6203 |
Popis: | Adolescent psychostimulant abuse has been on the rise over the past decade. This trend has demonstrable ramifications on adolescent behavior and brain morphology, increasing risk for development of addiction during adolescence and in later adulthood. Neuroimmune substrates are implicated in the etiology of substance use disorders. To add to this body of work, the current study was developed to explore the role of a chemokine receptor, CXC Chemokine Receptor 4 (CXCR4), in the development of amphetamine (AMPH) sensitization. We targeted CXCR4 as it is implicated in developmental processes, dopaminergic transmission, neuroimmune responses, and the potentiation of psychostimulant abuse pathology. To evaluate the role of CXCR4 activity on the development of AMPH sensitization, a CXCR4 antagonist (Plerixafor; AMD3100) was administered to rats as a pretreatment variable. Specifically, adolescent Long Evans male rats (N = 37) were divided into four groups: (1) AMD3100 (IP, 4.0 mg/kg) + AMPH (IP, 4.0 mg/kg), (2) saline (SAL; 0.9% NaCl) + AMPH, (3) AMD3100 + SAL, and (4) SAL + SAL. Animals were first habituated to locomotor activity (LMA) chambers, then injected with a pretreatment drug (AMD3100 or SAL) followed by AMPH or SAL every other for four days. After a one-week withdrawal period, all animals were administered a low challenge dose of AMPH (IP, 1.0 mg/kg). AMPH-injected rats displayed significantly more locomotor activity compared to controls across all testing days. CXCR4 antagonism significantly attenuated AMPH-induced locomotor activity. On challenge day, AMD3100 pre-treated animals exhibited diminutive AMPH-induced locomotor activity compared to SAL pre-treated animals. Postmortem analyses of brain tissue revealed elevated CXCR4 protein levels in the striatum of all experimental groups. Our results implicate CXCR4 signaling in the development of AMPH sensitization and may represent an important therapeutic target for future research in psychostimulant abuse. |
Databáze: | OpenAIRE |
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