Figure 4.

Sensitivity of cocaine self-administration, and insensitivity of PRE-084 self-administration to dopamine receptor antagonism. Rats were trained to self-administer cocaine (0.032–1.0 mg/kg/injection) under a fixed-ratio five-response schedule of reinforcement with different doses of cocaine available in five components. All antagonists except BD1063 (5 min before sessions) were administered intraperitoneally, 30 min before sessions. Each point represents the mean±SEM of response rates on the active lever. (a–c) Effects of antagonists selective for dopamine D₁-like receptors, SCH 39166, D₂-like receptors, L-741 626, and the combination of minimally active doses of each. SCH 39166 and L-741 626 shifted the cocaine self-administration dose–effect curve rightward and the combination produced an insurmountable antagonism over the range of tested doses of cocaine. (d) The non-selective dopamine receptor antagonist, haloperidol, produced a dose-related rightward shift in the cocaine self-administration dose–effect curve. (e) The σ₁R antagonist, BD1063, did not substantially affect cocaine self-administration. (f–h) The dopamine antagonists and their combination did not substantially affect PRE-084 self-administration. (i) Haloperidol dose-dependently decreased maximal PRE-084 self-administration. (j) BD1063 dose-dependently decreased maximal PRE-084 self-administration.