Figure 3.

Effects of the 5-HT_1B receptor antagonist SB 224289 administered alone (left) or in combination with CP 94,253 (right) on cocaine self-administration under a fixed ratio (FR) 5 schedule of reinforcement during maintenance. Data are expressed as the number of reinforcers obtained (±SEM) at a dose previously found to be on the descending (0.75 mg/kg/0.1 mL, i.v.) limb of the cocaine dose–effect function (see Figure 1). Prior to testing, there were no differences between SB 224289 and CP 94,253 groups in the number of cocaine reinforcers (0.75 mg/kg/0.1 mL, i.v.) obtained during cocaine self-administration training (data not shown). Rats (n = 8–10/5-HT_1B receptor ligand group) were pretreated with vehicle (1 mL/kg, s.c.; white bars) on one test day and their assigned 5-HT_1B receptor drug(s; black bars) [SB 224289 (2.5, 5.0, or 7.5 mg/kg, i.p.); CP 94,253 (5.6 mg/kg, s.c.); or CP 94,253 (5.6 mg/kg, s.c.) + SB 224289 (5 mg/kg, i.p.)] on the other test day, with order of pretreatment (i.e., vehicle or 5-HT_1B receptor ligand) counterbalanced. Each rat received two injections prior to the test: SB 224289 or vehicle 60 min prior to the test and CP 94,253 or vehicle 15 min prior to the test. There was a significant effect of 5-HT_1B receptor ligand pretreatment on cocaine intake [F(4, 40) = 3.45, p < 0.05]. Compared to vehicle pretreatment, CP 94,253 attenuated cocaine intake (p < 0.05). SB 224289 administered alone failed to alter cocaine intake, but blocked the attenuating effect of CP 94,253. Asterisk (*) represents a difference from vehicle pretreatment (Newman-Keuls, p < 0.05).