TY - JOUR
T1 - CXCR4 inhibition with AMD3100 attenuates amphetamine induced locomotor activity in adolescent Long Evans male rats
AU - Mason, Briana
AU - Calhoun, Corey
AU - Woytowicz, Victoria
AU - Pina, Latifa
AU - Kanda, Roshninder
AU - Dunn, Curtis
AU - Alves, Antonio
AU - Donaldson, S. Tiffany
N1 - Publisher Copyright:
Copyright: © 2021 Mason et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85102327566
UR - https://www.scopus.com/pages/publications/85102327566#tab=citedBy
U2 - 10.1371/journal.pone.0247707
DO - 10.1371/journal.pone.0247707
M3 - Article
C2 - 33647040
AN - SCOPUS:85102327566
SN - 1932-6203
VL - 16
JO - PLoS ONE
JF - PLoS ONE
IS - 3 March
M1 - e0247707
ER -