The cocaine compulsion zone theory explains the reinstatement of lever pressing behavior in rats in response to a single cocaine dose.

A single non-contingent dose of cocaine reinstates extinguished lever pressing behavior in rats trained to self-administer cocaine. This represents a model of relapse in cocaine use disorder and the number of lever presses has been the standard measure. Lever pressing behavior during self-administration occurs only when cocaine levels are below the satiety threshold and above the remission/priming threshold, a range termed the compulsion zone. Calculated cocaine levels at the time of each lever press during an FR1 self-administration session and following a single non-contingent dose of cocaine were compared. The mean latency to lever pressing behavior was dose dependent and ranged from 1 to 11 min after cocaine doses of 2 or 12 μmol/kg, respectively. This is consistent with higher cocaine doses producing levels above satiety threshold that take more time to fall back to that threshold. The level of cocaine when lever pressing occurred was similar whether cocaine was self-administered or after a single dose of cocaine. The number of lever presses after a single cocaine dose was variable and poorly dose dependent. The latency to the start of lever pressing behavior is a more reliable dependent measure than the number of lever presses. In addition, lever pressing behavior occurs only when cocaine levels are within the compulsion zone. The compulsion zone theory not only explains maintained cocaine self-administration behavior, but also explains the reinstatement of lever pressing behavior in response to a single non-contingent cocaine dose.