Ronald Keiflin1, Caroline Vouillac, Martine Cador. 1. CNRS-UMR 5227, team Neuropsychopharmacology of addiction, University Bordeaux 2, University Bordeaux 1, 146 rue Leo Saignat, 33076, Bordeaux Cedex, France. ronald.keiflin@etud.u-bordeaux2.fr
Abstract
RATIONALE: Extended cocaine self-administration has been shown to potentiate reinstatement. This increased vulnerability to relapse could be attributed not only to extended cocaine exposure but also to extended operant training. OBJECTIVE: This study was aimed at determining the influence of different operant training histories on cocaine-induced reinstatement when cocaine intake is kept constant. MATERIALS AND METHODS: Cocaine intake and operant training were dissociated by using experimental procedures generating different histories of operant training but almost identical histories of cocaine intake. Rats were first trained to self-administer cocaine at a classical unit dose (250 microg/inf, FR1), then in independent groups, the level of operant response was changed for the next 20 sessions by changing either the unit dose available (83, 250, or 750 microg/inf, Experiment 1) or the fixed ratio required (FR-1, FR-3, or FR-10, Experiment 2). Then, all rats were tested for reinstatement with different priming doses of cocaine (0, 5, 10, and 15 mg/kg; i.p.) at an early and late stage of an extinction period. RESULTS: Level of responding during training predicts the level of reinstatement later on, independently of the amount of cocaine consumed. High FR requirement and low unit dose access led to higher level of reinstatement at early and late stage of the extinction period, respectively. CONCLUSIONS: This study shows that the level of operant responding required to maintain optimal cocaine intake directly influences later levels of reinstatement. This finding suggests that environmental constrains that make drug-taking demanding and effortful may increase the vulnerability to relapse.
RATIONALE: Extended cocaine self-administration has been shown to potentiate reinstatement. This increased vulnerability to relapse could be attributed not only to extended cocaine exposure but also to extended operant training. OBJECTIVE: This study was aimed at determining the influence of different operant training histories on cocaine-induced reinstatement when cocaine intake is kept constant. MATERIALS AND METHODS:Cocaine intake and operant training were dissociated by using experimental procedures generating different histories of operant training but almost identical histories of cocaine intake. Rats were first trained to self-administer cocaine at a classical unit dose (250 microg/inf, FR1), then in independent groups, the level of operant response was changed for the next 20 sessions by changing either the unit dose available (83, 250, or 750 microg/inf, Experiment 1) or the fixed ratio required (FR-1, FR-3, or FR-10, Experiment 2). Then, all rats were tested for reinstatement with different priming doses of cocaine (0, 5, 10, and 15 mg/kg; i.p.) at an early and late stage of an extinction period. RESULTS: Level of responding during training predicts the level of reinstatement later on, independently of the amount of cocaine consumed. High FR requirement and low unit dose access led to higher level of reinstatement at early and late stage of the extinction period, respectively. CONCLUSIONS: This study shows that the level of operant responding required to maintain optimal cocaine intake directly influences later levels of reinstatement. This finding suggests that environmental constrains that make drug-taking demanding and effortful may increase the vulnerability to relapse.
Authors: Louk J M J Vanderschuren; Anton N M Schoffelmeer; Sarah D C Van Leeuwen; Liesbeth Hof; Allert J Jonker; Pieter Voorn Journal: Eur J Neurosci Date: 2002-12 Impact factor: 3.386