Ventral pallidal neurons code incentive motivation: amplification by mesolimbic sensitization and amphetamine.
Neurons in ventral pallidum fire to reward and its predictive cues. We tested mesolimbic activation effects on neural reward coding. Rats learned that a Pavlovian conditioned stimulus (CS+1 tone) predicted a second conditioned stimulus (CS+2 feeder click) followed by an unconditioned stimulus (UCS sucrose reward). Some rats were sensitized to amphetamine after training. Electrophysiological activity of ventral pallidal neurons to stimuli was later recorded under the influence of vehicle or acute amphetamine injection. Both sensitization and acute amphetamine increased ventral pallidum firing at CS+2 (population code and rate code). There were no changes at CS+1 and minimal changes to UCS. With a new 'Profile Analysis', we show that mesolimbic activation by sensitization/amphetamine incrementally shifted neuronal firing profiles away from prediction signal coding (maximal at CS+1) and toward incentive coding (maximal at CS+2), without changing hedonic impact coding (maximal at UCS). This pattern suggests mesolimbic activation specifically amplifies a motivational transform of CS+ predictive information into incentive salience coded by ventral pallidal neurons. Our results support incentive-sensitization predictions and suggest why cues temporally proximal to drug presentation may precipitate cue-triggered relapse in human addicts.
Tindell
Amy J
AJ
Department of Psychology, University of Michigan, Ann Arbor, MI 48109-0607, USA.
Berridge
Kent C
KC
Zhang
Jun
J
Peciña
Susana
S
Aldridge
J Wayne
JW
D000465:Algorithms; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003214:Conditioning, Classical; D003463:Cues; D004567:Electrodes, Implanted; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008032:Limbic System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D013239:Stereotyped Behavior / Q000187:drug effects
D000697:Central Nervous System Stimulants; D000661:Amphetamine