Effect of food training and training dose on nicotine self-administration in rats

Abstract

Few studies investigate factors that influence acquisition in nicotine self-administration (NSA), such as food training and training dose. Most have utilized peak doses along nicotine’s dose-response curve (15 and 30 μg/kg) that establish NSA in the majority of animals. To investigate the specific and combined effects of training and dose on NSA acquisition, separate and head-to head experiments using food training (FT) or spontaneous acquisition (SP) at multiple doses on the ascending limb of the dose-response curve were tested. First, rats underwent FT or SP under fixed ratio (FR1 and FR2) and progressive ratio (PR) schedules using 7.5–30 μg/kg nicotine. More rats acquired NSA with FT vs. SP at 3.75 μg/kg (56% vs. 38%) and 7.5 μg/kg (88% vs. 40%, p<0.05) and FT rats responded higher under PR. Based on these findings, rats then underwent identical NSA acquisition and PR (with and without nicotine), extinction and reinstatement induced by cue exposure and nicotine in a head-to-head comparison of FT and SP using 7.5 μg/kg. Acquisition differences were replicated: 100% FT and 60% SP rats met criteria (p<0.05). Without nicotine (cue only), no FT rats and 8% SP rats met criteria. FR and PR responding, extinction, and cue and nicotine-induced reinstatement did not differ between FT and SP. FT versus SP enhances acquisition at lower nicotine doses but does not alter subsequent behaviors. Lower doses can reinforce NSA and be used, in the absence of FT, to study influences on acquisition more closely modelling the initial phases of human smoking.

Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

“…Seven days after IV surgery, animals underwent NSA without food training ( Figure 1c) at three infusion doses (3.75, 7.5, or 15 µg/kg) that were found previously to fall along the ascending limb of nicotine's dose-response curve for spontaneous acquisition (Garcia et al, 2014). Rats underwent 2 hr daily NSA sessions under a FR1 schedule for 5 days and then a FR2 schedule for another 5 days, which was used to determine acquisition (Garcia et al, 2014;Shram et al, 2008).…”

“…Following recovery from IV surgery, rats (n=12/dose) underwent daily 1 hour NSA sessions under FR1 and FR2 for five days at a single nicotine dose of 7.5, 15, or 30 µg/kg ( Figure 1b). Rats then underwent a PR schedule of reinforcement at their same training dose, in 2 hour daily sessions for 5 sessions to create a baseline of responding, as previously described (Garcia et al, 2014). At 22 hours prior to the 6 th PR session all animals received one ICV injection of ACSF then underwent three PR sessions (sessions 6, 7, and 8).…”

“…Prior to surgery, rats were food trained to learn the self-administration operant behavior as previously described (Garcia et al, 2014). Following recovery from IV surgery, rats (n=12/dose) underwent daily 1 hour NSA sessions under FR1 and FR2 for five days at a single nicotine dose of 7.5, 15, or 30 µg/kg ( Figure 1b).…”

“…Seven days after ICV cannula implant, catheters were implanted into the right jugular vein as previously described (Garcia et al, 2014;Shram et al, 2008). To maintain patency, catheters were 7 flushed daily with sterile heparin in saline (0.1 ml, 50 U/ml).…”

“…Thiopental (2-4 mg, IV, 20 mg/ml) was used to test catheter patency after testing and non-patent animal data was removed from analysis. NSA was carried out in sixteen operant chambers operated by a computer-controlled interface system (Med Associates, St Albans, VT) under previously described conditions (Garcia et al, 2014).…”