The role of dopamine in learning, memory, and performance of a water escape task.
Dopamine-deficient (DD) mice have selective inactivation of the tyrosine hydroxylase gene in dopaminergic neurons, and they die of starvation and dehydration at 3-4 weeks of age. Daily injections of L-DOPA (50 mg/kg, i.p.) starting approximately 2 weeks after birth allow these animals to eat and drink enough for survival and growth. They are hyperactive for 6-9 h after receiving L-DOPA and become hypoactive thereafter. Because these animals can be tested in the presence or absence of DA, they were used to determine whether DA is necessary for learning to occur. DD mice were tested for learning to swim to an escape platform in a straight alley in the presence (30 min after an L-DOPA injection) or absence (22-24 h after an L-DOPA injection) of dopamine. The groups were split 24 h later and retested 30 min or 22-24 h after their last L-DOPA injection. In the initial test, DD mice without dopamine showed no evidence of learning, whereas those with dopamine had a learning curve similar in slope to controls but significantly slower. A retest after 24 h showed that DD mice can learn and remember in the absence of dopamine, leading to the inference that the lack of dopamine results in a performance/motivational decrement that masks their learning competence for this relatively simple task.
Denenberg
Victor H
VH
Department of Biochemistry, University of Washington, Box 357370, Seattle, WA 98195-7370, USA. denenberg@mac.com
Kim
Douglas S
DS
Palmiter
Richard D
RD
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D015259:Dopamine Agents; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine