Send to

Choose Destination
See comment in PubMed Commons below
Psychopharmacology (Berl). 2007 Apr;191(3):567-78. Epub 2006 Nov 9.

Viral restoration of dopamine signaling to the dorsal striatum restores instrumental conditioning to dopamine-deficient mice.

Author information

Graduate program in Neurobiology & Behavior, Howard Hughes Medical Institute, University of Washington, Seattle, WA, 98195, USA.



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.


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.


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.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer
    Loading ...
    Support Center