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Animal Experimental Models

開催日 2014/9/13
時間 18:10 - 19:10
会場 Room H(304)
Chairperson(s) 渡我部 昭哉 / Akiya Watakabe (基礎生物学研究所 脳生物学研究部門 / Division of Brain Biology, National Institute for Basic Biology, Japan)
西川 徹 / Toru Nishikawa (東京医科歯科大学 大学院 精神行動医科学分野 / Section of Psychiatry and Behavioral sciences, Graduate School of Medical and Dental Sciences,Tokyo Medical and Dental University, Japan)

Extinction of fear and drug-seeking during adolescence

  • O3-H-6-1
  • Jee Hyun Kim:1 
  • 1:University of Melbourne, Australia 

It is widely agreed that adolescence is a particularly vulnerable age for both anxiety and addiction. I have accumulated powerful evidence that adolescents are significantly impaired in extinction of both cocaine- and shock-related cues, which may explain adolescent vulnerability to anxiety and addiction. Extinction forms the basis of exposure therapies that inhibit the salience of the cues and the environments associated with a fearful event, or drug use. I have shown that pre-adolescent (P24), adolescent (P35), and adult (P70) rats express identical fear conditioning and extinction acquisition. When tested the next day, however, adolescent rats showed almost complete failure to show long-term extinction compared to P24 and P70 rats. Consistent with the fear data, when P34 (adolescent) and P69 (adult) rats received CS extinction following a period of cocaine self-administration, prior CS extinction proved effective in reducing CS-induced reinstatement in adults, but not in adolescents. A likely explanation for the differential extinction observed in adolescents relates to how dopaminergic signaling in the adolescent PFC is dominated by D1R compared to D2R. Indeed, when we increased D2R activity via systemic injection of the selective D2 partial-agonist Aripiprazole, CS extinction appears to be facilitated, evidence by the reduced fear or drug-seeking CR when tested drug-free the next day. These behavioral findings were accompanied with changes in activation of neurons in the PFC that receive dopaminergic innervation.

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