Beschreibung:
<jats:p>Cannabinoid administration prior to opioid administration can produce opioid‐sparing antinociceptive effects in several species by reducing the dosage of opioid needed to produce effective antinociception. These potentially valuable clinical effects could be undermined, however, if the cannabinoids also enhance the disruptive effects of opioids on neurobehavioral function. To address this question, the combined effects of THC and heroin were examined in nonhuman primates (rhesus macaques, n=4) responding in a learning and performance task and concurrently exposed to a tail‐withdrawal antinociception procedure. Testing in this case was facilitated by examining 4 discrete cycles of acquisition and performance that were separated by timeout periods to facilitate tail‐withdrawal tests and cumulative dosing. Each cycle included a 10‐min time out period for drug onset, a 15‐min acquisition component, and a 5‐min performance component. In the learning and performance task, subjects acquired a new 5‐response key‐sequence, or emitted a well‐rehearsed 5‐response key‐sequence, respectively. Responding in both components of the task was reinforced with a food pellet after every three completions of the sequence (i.e., a second‐order fixed‐ratio [FR3] schedule of food reinforcement). Warm‐water tail‐withdrawal antinociception was measured using three water temperatures (40°, 50°, and 55°C). Heroin alone dose‐dependently decreased response rates in the acquisition and performance components without markedly increasing percent errors. When the opioid antagonist naltrexone (1 mg/kg) preceded the cumulative heroin injections, the heroin dose‐effect curves for both the behavioral disruptions and antinociception were shifted rightward indicating both effects were mediated by mu‐opioid receptors. In contrast, THC alone disrupted both behaviors at doses that had no antinociceptive effect, but it shifted the heroin dose‐effect curves for learning, performance, and antinociception leftward. Overall, these data demonstrate that THC produces its opioid‐sparing antinociceptive effects at doses that are behaviorally disruptive alone and in combination with heroin.</jats:p><jats:p><jats:bold>Support or Funding Information</jats:bold></jats:p><jats:p>This work was supported by a National Institute of Drug Abuse Fellowship (F32DA47013‐01)</jats:p><jats:p>This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in <jats:italic>The FASEB Journal</jats:italic>.</jats:p>