Cadoni C, Solinas M, Di Chiara G
Department of Toxicology and CNR Center for Neuropharmacology, University of Cagliari, Viale Diaz 182-09126, Cagliari, Italy.
Eur J Pharmacol. 2000 Jan 24;388(1):69-76. doi: 10.1016/s0014-2999(99)00824-9.
The nucleus accumbens has been subdivided into a shell and a core compartment on the basis of histochemical and connectional differences. Recently, we reported that behavioral sensitization to morphine is associated with an increased dopamine transmission in the caudate-putamen and in the nucleus accumbens core as well as a decreased response in the nucleus accumbens shell following acute morphine challenge. We have now performed a similar study in rats sensitized to amphetamine and to cocaine. Behavioral sensitization was induced by daily administration of a single dose of 1 mg/kg s.c. of amphetamine for 10 days or of 10 mg/kg i.p. of cocaine twice a day for 14 days. Microdialysis was performed 10-14 days after the last injection of amphetamine and 7-10 days after the last injection of cocaine. Both schedules resulted in robust behavioral sensitization in response to challenge with 0.25 and 0.5 mg/kg of amphetamine and to 5 and 10 mg/kg of cocaine, respectively. Subjects pre-exposed to amphetamine showed a sensitization of dopamine transmission in the nucleus accumbens core but not in the nucleus accumbens shell. Subjects pre-exposed to cocaine showed sensitization of dopamine transmission in the core only to the lower dose of cocaine. In the shell no change was observed after the lower dose of cocaine while a significant reduction of the dopamine response was observed after the higher dose. These results suggest that behavioral sensitization might result from reciprocal changes in the response of nucleus accumbens dopamine in the shell and in the core to drug challenge.
基于组织化学和连接差异，伏隔核已被细分为壳区和核心区。最近，我们报道，对吗啡的行为敏化与尾状核 - 壳核以及伏隔核核心中多巴胺传递增加有关，同时在急性吗啡激发后伏隔核壳区的反应降低。我们现在对苯丙胺和可卡因致敏的大鼠进行了类似的研究。通过每天皮下注射1mg/kg苯丙胺，连续10天或每天腹腔注射10mg/kg可卡因，每天两次，连续14天来诱导行为敏化。在最后一次注射苯丙胺后10 - 14天和最后一次注射可卡因后7 - 10天进行微透析。两种给药方案分别导致对0.25mg/kg和0.5mg/kg苯丙胺以及5mg/kg和10mg/kg可卡因激发的强烈行为敏化。预先接触苯丙胺的动物在伏隔核核心中显示多巴胺传递敏化，但在伏隔核壳区未显示。预先接触可卡因的动物仅在核心中对较低剂量的可卡因显示多巴胺传递敏化。在壳区，较低剂量的可卡因后未观察到变化，而较高剂量后观察到多巴胺反应显著降低。这些结果表明，行为敏化可能是由于伏隔核壳区和核心区中多巴胺对药物激发的反应相互变化所致。
