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
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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