Exercise craving potentiates excitatory inputs to ventral tegmental area dopaminergic neurons. (5th October 2020)

• Record Type: Journal Article
• Authors: Medrano, Maria‐Carmen; Hurel, Imane; Mesguich, Emma; Redon, Bastien; Stevens, Christopher; Georges, François; Melis, Miriam; Marsicano, Giovanni; Chaouloff, Francis
• Is Part Of: Addiction biology. Volume 26:Number 3(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-05
• Subjects: AMPAR/NMDAR ratio -- dopamine -- motivation -- reinstatement -- synaptic plasticity -- wheel‐running; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12967
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: Physical exercise, which can be addictogenic on its own, is considered a therapeutic alternative for drug craving. Exercise might thus share with drugs the ability to strengthen excitatory synapses onto ventral tegmental area (VTA) dopaminergic neurones, as assessed by the ratio of AMPA receptor (AMPAR)‐mediated excitatory postsynaptic currents (EPSCs) to NMDA receptor (NMDAR)‐mediated EPSCs. As did acute cocaine, amphetamine, or Δ 9 ‐tetrahydrocannabinol (THC) pretreatments, an acute 1‐h wheel‐running session increased the AMPAR/NMDAR ratio in VTA dopaminergic neurones. To dissect the respective influences of wheel‐running seeking and performance, mice went through an operant protocol wherein wheel‐running was conditioned by nose poking under fixed ratio schedules of reinforcement. Conditioned wheel‐running increased the AMPAR/NMDAR ratio to a higher extent than free wheel‐running, doing so although running performance was lower in the former paradigm than in the latter. Thus, the cue‐reward association, rather than reward consumption, played a major role in this increase. The AMPAR/NMDAR ratio returned to baseline levels in mice that had extinguished the cued‐running motivated task, but it increased after a cue‐induced reinstatement session. The amplitude of this increase correlated with the intensity of exercise craving, as assessed by individual nose poke scores. Finally, cue‐induced reinstatement of running seeking proved insensitive to acute cocaine or THC pretreatments. Our study reveals for the first time that the drive for exercise bears synaptic influences on VTA dopaminergic neurones which are reminiscent of drug actions. Whether these influences play a role in the therapeutic effects of exercise in human drug craving remains to be established. Abstract : This study compared the respective effects of free and conditioned wheel‐running on the ratio of AMPA receptor (AMPAR)‐mediated excitatory postsynaptic currents (EPSCs) to NMDA receptor (NMDAR)‐mediated EPSCs in ventral tegmental area dopaminergic neurones. Conditioned wheel‐running increased the AMPAR/NMDAR ratio to a higher extent than free wheel‐running although running performance was lower. The AMPAR/NMDAR ratio increased after a cue‐induced reinstatement session of running seeking, and the amplitude of this increases being correlated with the intensity of exercise craving.