Viral restoration of dopamine signaling to the dorsal striatum restores instrumental conditioning to dopamine-deficient mice.
BACKGROUND
Instrumental responding was evaluated to determine whether mice lacking dopamine [dopamine-deficient mice (DD mice)] could learn to preferentially press a visually cued, active lever for food reward over an inactive lever.


RESULTS
When DD mice were treated with 3,4-L: -dihydroxyphenalanine (L-dopa) to restore dopamine signaling systemically, they were able to learn to press the active lever as well as control mice, whereas mice lacking dopamine would not perform the task. Importantly, DD mice treated with caffeine (to stimulate locomotor and feeding behaviors) also failed to show preference for the active lever and were slower to retrieve rewards after making a reinforced operant response. Selective restoration of dopamine signaling to the nigrostriatal pathway of DD mice via viral-mediated gene transfer completely restored learning and performance of this simple instrumental task. Furthermore, the virally treated DD mice were willing to lever press as much as control mice for reward in progressive-ratio and high fixed-ratio schedules of reinforcement.


CONCLUSIONS
These results suggest that the deficit in goal-directed behavior observed in mice without dopamine signaling is the result of decreased motivation to obtain reward, and that dopamine signaling in the dorsal striatum is sufficient to restore normal goal-directed behavior on a variety of operant responding tasks.
Robinson
Siobhan
S
Graduate program in Neurobiology & Behavior, Howard Hughes Medical Institute, University of Washington, Seattle, WA, 98195, USA.
Rainwater
Aundrea J
AJ
Hnasko
Thomas S
TS
Palmiter
Richard D
RD
D006516:Adenoviruses, Canine / Q000235:genetics*; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003463:Cues; D004298:Dopamine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency / Q000235:genetics; D005247:Feeding Behavior; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009042:Motivation; D009043:Motor Activity; D012055:Reinforcement Schedule; D012201:Reward; D013378:Substantia Nigra / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency / Q000235:genetics
D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D002110:Caffeine; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine