The central neuroimmune microenvironment plays a regulatory role in substance use disorders. Clinical populations that experience issues with anxiety also show high comorbid rates of substance abuse. We hypothesize that exposure to drugs of abuse initiates a proinflammatory cascade that first activates toll-like receptors which results in increased levels of proinflammatory cytokines and other innate immune factors that are thought to contribute to mesocorticolimbic neuroplasticity. The present study examined differences in toll-like receptor 4 (TLR4) protein levels in adolescent male Long-Evans rats (N=30) phenotyped as showing high (HAn) and low (LAn) anxiety-like behavior after exposure to an amphetamine sensitization regimen. Anxiety phenotypes were screened using the elevated plus maze (EPM), and values on the EPM measured included percent open arm (OA) entries and time spent on the OA. We employed a quartile analysis on the EPM values, with the upper quartile categorized as LAn, and values in the lower quartile categorized as HAn. Male HAn adolescents exhibited the most hyperactivity to the locomotor-activating effects of acute and 4-day amphetamine (4.0 mg/kg IP). Male HAn lines displayed the greatest locomotor response to a low challenge dose of AMPH (1.0 mg/kg IP) after a 7-day withdrawal period. Evaluation of TLR4 protein levels are currently underway, but preliminary analysis provides evidence for greater TLR4 protein levels in the amygdala of HAn adolescent males. HAn profiles map on to amphetamine sensitivity and may be a viable tool for investigations of the role of neuroinflammation in mediating the neuroplasticity important for sensitization and relapse vulnerability.
Corey Calhoun– Graduate Student, University of Massachusetts, Boston
Brooke Plotkin– Graduate Student, University of Massachusetts, Boston
Latifa Pina– Undergraduate Research Assistant, University of Massachusetts, Boston
Antonio Alves– Undergraduate Research Assistant, University of Massachusetts, Boston
S. Tiffany Donaldson– Principal Investigator, University of Massachusetts, Boston