Effect of the Toll-like receptor 4 antagonist (+)- naltrexone on incubation of heroin craving
Wednesday, Oct 17, 2012, 3:00 PM - 4:00 PM
, H. EICHENBAUM
, C. L. PICKENS
, J. M. BOSSERT
, K. RICE
, L. R. WATKINS
, Y. SHAHAM
, *F. R. THEBERGE
NIH/NIDA BRC, Baltimore, MD;
Natl. Inst. on Alcohol Abuse and Alcoholism, Natl. Inst. of Hlth., Rockeville, MD;
Dept. Psychology & Neurosci., Univ. Colorado At Boulder, Boulder, CO
Recent evidence implicates the glial toll-like receptor 4 (TLR4) in morphine analgesia, tolerance, and reward, as assessed in the conditioned place preference procedure. Here we used the selective TLR4 antagonist (+)-naltrexone (a µ-opioid receptor inactive isomer) to determine the role of this receptor in the time-dependent increases in cue-induced heroin seeking during forced abstinence (incubation of heroin craving). We trained rats for 9 h/day to self-administer heroin (0.1 mg/kg/infusion) for 9 days; lever presses were paired with a 5-sec tone-light cue. We then assessed cue-induced heroin seeking in 30-min extinction sessions on abstinence day 1; immediately after testing, we implanted the rats with Alzet minipumps delivering (+)-naltrexone (0, 15.0, or 30.0 mg/kg/day, s.c) for 14 days. We then tested the rats for incubated cue-induced heroin seeking in 3-h extinction tests on abstinence day 13. We found that both doses of (+)-naltrexone decreased cue-induced heroin seeking on abstinence day 13. Results suggest a critical role of the glial TLR4 in the development of incubation of heroin craving. We currently study the effect of acute injections of (+)-naltrexone on incubation of heroin craving.
TOLL-LIKE RECEPTOR 4
[Authors]. [Abstract Title]. Program No. XXX.XX. 2012 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2012. Online.
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