Figure 2.

Antagonizing the CB1 receptor or preventing 2-AG mobilization in the VTA prevents cocaine-mediated increases in motivation. (A) Intracranial administration of vehicle (0.5 ul/side, IC) or rimonabant (0.5 and 1 ug/0.5 ul/side, IC) did not change the breakpoints or total number of reinforcers earned compared to baseline sessions (n = 25; 11 males, 14 females). (B) Increases in motivation following 10 mg/kg (IP) cocaine are reversed by intra-VTA administration of rimonabant (1 ug/0.5 ul/side, IC) (n = 22; 11 males, 11 females). (C) Although the intra-VTA administration of rimonabant (1 ug/0.5 ul/side, IC) did not significantly reduce motivation enhanced by 15 mg/kg (IP) cocaine, it reduced the number of reinforcers to baseline levels (n = 20; 11 males, 9 females). (D) Schematic of intracranial (IC) and systemic (IP) injections. (E) Intracranial administration of vehicle (0.5 ul/side, IC) or THL (5 ug/0.5 ul/side, IC) did not change the breakpoints or total number of reinforcers compared to baseline sessions (n = 20; 10 males, 10 females). (F) Intra-VTA THL administration reverses increases in motivation due to 10 mg/kg (IP) cocaine (n = 17; 8 males, 9 females). (G) Intra-VTA THL administration reverses increases in motivation due to 15 mg/kg (IP) cocaine (n = 15; 9 males, 6 females). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001