大約八周大的C57BL/6公鼠，每天腹腔注射一劑古柯鹼 (10 mg/kg)和甲基安非他命 (1 mg/kg)，持續三天，能夠有效地建立制約性場地偏好。在大約24小時前腹腔注射粗糠柴毒素 (5 mg/kg)，可以有效的影響前述的制約性場地偏好的建立。制約性場地偏好建立後，連續三天的生理食鹽水腹腔注射，來撲滅小鼠對於制約性場地偏好的記憶。在腹腔注射生理食鹽水前大約20小時前給予單一劑的粗糠柴毒素，並不能夠影響到往後的制約性場地偏好的記憶抹除現象，但能夠影響往後的藥物以及壓力所產生的復發現象。但是單獨給予一劑粗糠柴毒素，並不能夠使小鼠抹除對於制約性場地偏好的記憶。而單一劑的粗糠柴毒素注射，能夠使的小鼠大腦內海馬迴腦源性神經營養因子表達長效的快速上升，但並沒有影響到磷酸化的ERK 和 CREB。預先處理腦源性神經營養因子TrkB受體拮抗劑，K252a (5 µg/kg)，也不會影響粗糠柴毒素對於制約性場地偏好的抑制效果。在每次調節前給予選擇性TrkB激動劑，7,8-二羥基黃酮(10 mg/kg x 6)，並不會影響到制約性場地偏好的建立。基於這些研究結果，表明全身性的粗糠柴毒素給予能夠有效的促進古柯鹼以及甲基安非他命的儲存器的抹除。

關鍵字：粗糠柴毒素; 甲基安非他命; 古柯鹼; 制約; 記憶; 腦源性神經營養因子

Three cocaine (10 mg/kg/conditioning, COC)- and methamphetamine (1 mg/kg/conditioning, MA)-place conditionings reliably established the drug-induced conditioned place preference (CPP) in 8-week-old male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 hrs prior to the first COC- and MA-place conditioning prevented the establishment of COC and MA-induced CPP. Following the establishment of the COC- and MA-induced CPP, three consecutive daily saline-place conditionings were used to extinguish mouse CPP performance. A single rottlerin injection (5 mg/kg, i.p.) 20 hrs prior to the first saline-place conditioning bout did not affect such conditionings-produced CPP extinction but diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Omitting the extinction conditionings, a single rottlerin injection (5 mg/kg) did not cause the conditionings-produced CPP extinction. A single rottlerin (5 mg/kg, i.p.) treatment produced fast-onset and long-lasting increases in hippocampal BDNF levels, while such a treatment did not alter ERK and CREB phosphorylation in the hippocampus. Pretreatment with a BDNF TrkB receptor antagonist, K252a (5 µg/kg), did not affect rottlerin’s suppressing effect on cocaine-induced CPP. Treatment with 7,8-dihydroxyflavone (10 mg/kg x 6), a selective TrkB agonist, prior to each conditioning bout did not affect COC-induced CPP. Based on these results, suggest that systemic rottlerin treatment may be beneficial in facilitating the erasure of COC and MA-supported memory. Importantly, such a treatment may afford a therapeutic advance in corroborating the extinction training-caused forgetting of the COC and MA-supported memory. However, rottlerin-produced brain BDNF increases play a negligible role in mediating its effects on the formation and maintenance of psychostimulant-supported memory in this regard.

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