Figure 4.
Clofibrate had a protective effect in models of nicotine- and cue-induced relapse in squirrel monkeys. (a) Nicotine-induced reinstatement. A baseline of nicotine abstinence and low rates of nicotine seeking was arranged by substituting saline for nicotine in the intravenous self-administration procedure. During test sessions, a priming injection of nicotine was given automatically before the session. When monkeys were given only clofibrate's vehicle before the nicotine priming injection (‘Veh+Nic' condition), the nicotine prime significantly reinstated nicotine-seeking behavior. However, when monkeys were given 100 mg/kg clofibrate 100 min before the priming injection (‘Clof+Nic' condition), nicotine-seeking was not reinstated. MK886 reversed this effect of clofibrate partially at a dose of 1 mg/kg (‘MK1+Clof+Nic' condition) and fully at 3 mg/kg (‘MK3+Clof+Nic' condition). On the baseline day before each test session, monkeys were given clofibrate's vehicle followed by a saline injection instead of a nicotine prime; data from these sessions were combined across days (‘Veh+Saline' condition). *Significant difference from ‘Veh+Saline' condition. #Significant difference from ‘Clof+Nic' condition. (b) Cue-induced reinstatement. A baseline of nicotine abstinence and low rates of nicotine seeking was arranged by discontinuing intravenous injections and the presentation of visual cues (‘Veh' condition). During test sessions, cue presentation was reinstituted, and responding produced intravenous saline injections. The cues significantly reinstated nicotine seeking when monkeys were treated with vehicle (‘Veh+Cues' condition), but this effect was significantly blocked by treatment with 100 mg/kg clofibrate (‘Clof+Cues' condition). *Significant difference from ‘Veh' condition. #Significant difference from ‘Clof+Cues' condition; n=4 for nicotine-induced reinstatement and n=3 for cue-induced reinstatement. In all, 10 lever responses were required for each saline injection, and sessions lasted 1 h. Data for ‘Veh' (black bar) in panel b represent number of responses divided by 10, as no injections or timeouts were given in this condition. All data were presented as mean±SEM.