title: Requirement of dopamine signaling in the amygdala and striatum for learning and maintenance of a conditioned avoidance response.
abstract: Two-way active avoidance (2WAA) involves learning Pavlovian (association of a sound cue with a foot shock) and instrumental (shock avoidance) contingencies. To identify regions where dopamine (DA) is involved in mediating 2WAA, we restored DA signaling in specific brain areas of dopamine-deficient (DD) mice by local reactivation of conditionally inactivated Th genes using viral gene therapy. Among all targeted areas--prefrontal cortex (PFC), amygdala, ventral striatum, dorsal striatum, and whole striatum--only restoration of DA signaling to both the whole striatum together with the amygdala enabled DD mice to acquire 2WAA. However, after prolonged overtraining during which DD mice had DA synthesis systemically reconstituted pharmacologically with L-3,4-dihydroxyphenylalanine (L-Dopa), DA signaling in the striatum alone was sufficient to maintain 2WAA, whereas DA signaling in the PFC together with the amygdala was insufficient to maintain 2WAA. Our results indicate that learning 2WAA requires DA signaling in both the amygdala and the entire striatum; however, after sufficient training, DA signaling in the striatum alone can maintain the learned avoidance behavior.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Darvas
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Fadok
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D002110:Caffeine / Q000494:pharmacology; D051243:Caveolin 2 / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005239:Fear; D007980:Levodopa / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D011930:Reaction Time / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency / Q000378:metabolism
chemical_list: C495545:Cav2 protein, mouse; D051243:Caveolin 2; D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D002110:Caffeine; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine