Dopamine Receptor Antagonist‐Induced Elevation of the Compulsion Zone Results in Differential Effects on Cocaine Self‐Administration and Lever‐Pressing Behavior

Abstract

Dopamine receptor antagonists raise both the cocaine priming and satiety thresholds (the lower and upper limits of the compulsion zone, respectively), so antagonists will decrease the probability of cocaine priming self‐administration behavior. However, if priming occurs in the presence of dopamine receptor antagonists, then cocaine consumption will accelerate. The compulsion zone also explains the lever‐pressing after access to cocaine is terminated, but the effects of antagonists on the compulsion zone are unexplored. The compulsion zone theory predicts that antagonists will decrease the duration of unloading activity. Male rats were trained to self‐administer cocaine on an FR1 schedule. Upon lever‐pressing, a unit dose (3 umol/kg i.v.) was administered. The dopamine receptor antagonists, SCH23390 (10‐30 nmol/kg), eticlopride (10‐30 nmol/kg), or molindone (750‐3000 nmol/kg) were administered i.v. either while cocaine was accessible during the maintenance phase or following termination of access denoting the start of the unloading phase. The lever‐pressing activity was recorded during the unloading phase. Antagonists accelerated self‐administration during the maintenance phase due to the elevated satiety threshold, consistent with previous studies. Antagonists administered immediately prior to the unloading phase shortened the duration of lever‐pressing, and lever‐pressing began at a higher calculated cocaine level. This is consistent with the antagonists elevating the compulsion zone. The faster elimination of cocaine at these elevated levels results in cocaine levels transiting the compulsion zone more rapidly. The differential effect of dopamine receptor antagonists on lever‐pressing behavior may provide insights to the appropriate use of antagonists as medications for cocaine use disorder.