Persistent palatable food preference in rats with a history of limited and extended access to methamphetamine self-administration

Abstract

Recent studies have shown that when given a mutually exclusive choice between cocaine and palatable foods, most rats prefer the non-drug rewards over cocaine. Here, we used a discrete choice procedure to assess whether palatable food preference generalizes to rats with a history of limited (3 hours/day) or extended (6 or 9 hours/day) access to methamphetamine self-administration. On different daily sessions, we trained rats to lever-press for either methamphetamine (0.1-0.2 mg/kg/infusion) or palatable food (five pellets per reward delivery) for several weeks; regular food was freely available. We then assessed food-methamphetamine preference either during training, after priming methamphetamine injections (0.5-1.0 mg/kg), following a satiety manipulation (palatable food exposure in the home cage) or after 21 days of withdrawal from methamphetamine. We also assessed progressive ratio responding for palatable food and methamphetamine. We found that independent of the daily drug access conditions and the withdrawal period, the rats strongly preferred the palatable food over methamphetamine, even when they were given free access to the palatable food in the home cage. Intake of methamphetamine and progressive ratio responding for the drug, both of which increased or escalated over time, did not predict preference in the discrete choice test. Results demonstrate that most rats strongly prefer palatable food pellets over intravenous methamphetamine, confirming previous studies using discrete choice procedures with intravenous cocaine. Results also demonstrate that escalation of drug self-administration, a popular model of compulsive drug use, is not associated with a cardinal feature of human addiction of reduced behavioral responding for non-drug rewards.

Keywords: Discrete choice; drug priming; extended access; food satiety; limited access; palatable food; preference; progressive ratio; psychostimulants; self-administration.

Figure 1. Apparatus

We equipped each chamber with a stainless steel grid floor (1) and two panels placed on the left and right walls. Left panel: Methamphetamine discriminative stimulus, red light (2), methamphetamine-paired active lever (retractable) (3), methamphetamine-paired cue light (4). We delivered the drug through an infusion pump (5) with a modified cannula (Plastics One) connected to a liquid swivel (6) via polyethylene-50 tubing that was protected by a metal spring (7). Right panel: Food discriminative stimulus, white light (8), food-paired active lever (retractable) (9), food-paired tone cue (10), food receptacle (11), and inactive (stationary) lever (12). We delivered food pellets through a food dispenser (13), connected by a rubber tube both located outside of the chamber. We placed a bottle of water (14) and a food hopper (15) on the external and internal side of the chamber’s transparent polycarbonate door, respectively. We enclosed the apparatus inside a sound-attenuating cubicles fitted with a fan (16).

Figure 2. Palatable food preference after limited access (3 hr/day) to methamphetamine self-administration

(A) Timeline of the experiment. (B) Self-administration: Mean±SEM number of food rewards (5 palatable food pellets/reward delivery) or methamphetamine infusions (0.1 mg/kg/infusion) during the 3 hr sessions. (C) Progressive ratio tests: Mean±SEM of the final ratio completed for food reward or methamphetamine infusions. (D) Discrete choice tests: Mean±SEM of food reward and methamphetamine infusions earned during the choice sessions (18 trials every 10 min): Left: Initial choice sessions (baseline) and a choice session after 21 withdrawal days; Middle: Effect of methamphetamine priming on reward choice; Right: Effect of increasing the duration of palatable pellets availability in the home cage on reward choice. * Different from the indifference level, p<0.05); ^# Different from the first session, p<0.05).

Figure 3. Palatable food preference during limited (3 hr/day) and extended access (6 hr/day) to methamphetamine self-administration

(A) Timeline of the experiment. (B) Self-administration: Mean±SEM number of food rewards (5 palatable food pellets/reward delivery) or methamphetamine infusions (0.1 or 0.2 mg/kg/infusion) during the alternate 3 hr/day and 6 hr/day training sessions(C) Discrete choice tests: Mean±SEM of food reward and methamphetamine infusions earned during the choice sessions (18 trials every 10 min). * Different from the indifference level, p<0.05. ^# Different from the first choice session, p<0.01).

Figure 4. Strong food preference during extended access (9 hr/day) to methamphetamine self-administration

(A) Timeline of the experiment. (B) Self-administration: Mean±SEM number of food rewards (5 palatable food pellets/reward delivery) or methamphetamine infusions (0.1 mg/kg/infusion) during the 9 hr sessions. (C) Progressive ratio tests: Mean±SEM of the final ratio completed for food reward or methamphetamine infusions. (D) Discrete choice tests: Mean±SEM of food reward and methamphetamine infusions earned during the choice sessions (20 trials every 10 min) * Different from the indifference level, p<0.05. ^# Different from the first session, p<0.01).

Figure 5. Strong food preference after reversal of the training conditions (9 hr/day sessions)

(A) Timeline of the experiment. (B) Self-administration: Mean±SEM number of food rewards (5 palatable food pellets/reward delivery) or methamphetamine infusions (0.1 mg/kg/infusion) during the 9 hr sessions. (C) Progressive ratio tests: Mean±SEM of the final ratio completed for food reward or methamphetamine infusions. (D) Discrete choice tests: Mean±SEM of food reward and methamphetamine infusions earned during the choice sessions (20 trials every 10 min). * Different from the indifference level, p<0.05). ^# Different from the first session (p<0.001).