Florence Allain1, Karim Bouayad-Gervais1, Anne-Noël Samaha2,3. 1. Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montreal, QC, H3C 3J7, Canada. 2. Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montreal, QC, H3C 3J7, Canada. Anna.samaha@umontreal.ca. 3. CNS Research Group, Faculty of Medicine, Université de Montréal, Montreal, QC, H3C 3J7, Canada. Anna.samaha@umontreal.ca.
Abstract
RATIONALE: Taking high and increasing amounts of cocaine is thought to be necessary for the development of addiction. Consequently, a widely used animal model of drug self-administration involves giving animals continuous drug access during long sessions (LgA), as this produces high and escalating levels of intake. However, human cocaine addicts likely use the drug with an intermittent rather than continuous pattern, producing spiking brain cocaine levels. OBJECTIVES: Using an intermittent-access (IntA) cocaine self-administration procedure in rats, we studied the relationship between escalation of cocaine intake and later incentive motivation for the drug, as measured by responding under a progressive ratio schedule of cocaine reinforcement. RESULTS: First, under IntA, rats escalated their cocaine use both within and between sessions. However, escalation did not predict later incentive motivation for the drug. Second, incentive motivation for cocaine was similar in IntA-rats limited to low- and non-escalating levels of drug intake (IntA-Lim) and in IntA-rats that took high and escalating levels of drug. Finally, IntA-Lim rats took much less cocaine than rats given continuous drug access during each self-administration session (LgA-rats). However, IntA-Lim rats later responded more for cocaine under a progressive ratio schedule of reinforcement. CONCLUSIONS: Taking large and escalating quantities of cocaine does not appear necessary to increase incentive motivation for the drug. Taking cocaine in an intermittent pattern-even in small amounts-is more effective in producing this addiction-relevant change. Thus, beyond the amount of drug taken, the temporal kinetics of drug use predict change in drug use over time.
RATIONALE: Taking high and increasing amounts of cocaine is thought to be necessary for the development of addiction. Consequently, a widely used animal model of drug self-administration involves giving animals continuous drug access during long sessions (LgA), as this produces high and escalating levels of intake. However, humancocaine addicts likely use the drug with an intermittent rather than continuous pattern, producing spiking brain cocaine levels. OBJECTIVES: Using an intermittent-access (IntA) cocaine self-administration procedure in rats, we studied the relationship between escalation of cocaine intake and later incentive motivation for the drug, as measured by responding under a progressive ratio schedule of cocaine reinforcement. RESULTS: First, under IntA, rats escalated their cocaine use both within and between sessions. However, escalation did not predict later incentive motivation for the drug. Second, incentive motivation for cocaine was similar in IntA-rats limited to low- and non-escalating levels of drug intake (IntA-Lim) and in IntA-rats that took high and escalating levels of drug. Finally, IntA-Lim rats took much less cocaine than rats given continuous drug access during each self-administration session (LgA-rats). However, IntA-Lim rats later responded more for cocaine under a progressive ratio schedule of reinforcement. CONCLUSIONS: Taking large and escalating quantities of cocaine does not appear necessary to increase incentive motivation for the drug. Taking cocaine in an intermittent pattern-even in small amounts-is more effective in producing this addiction-relevant change. Thus, beyond the amount of drug taken, the temporal kinetics of drug use predict change in drug use over time.
Entities:
Keywords:
Addiction; Binge-like cocaine intake; Escalation of cocaine intake; Intermittent access; Intravenous drug self-administration; Long access; Progressive ratio
Authors: Erin S Calipari; Mark J Ferris; Cody A Siciliano; Benjamin A Zimmer; Sara R Jones Journal: J Pharmacol Exp Ther Date: 2014-02-24 Impact factor: 4.030