Univ. Bordeaux, INCIA, UMR 5287, F-33000, Bordeaux, France.
Psychopharmacology (Berl). 2014 Oct;231(20):3965-72. doi: 10.1007/s00213-014-3534-1. Epub 2014 Apr 1.
The intake of psychostimulant drugs may induce cognitive dysfunction and negative affective-like states, and is associated with increased activity of stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates neuroendocrine, behavioural and autonomic responses to stressors, and might be implicated in substance-related disorders. CRF signalling is mediated by two receptor types, named CRF1 and CRF2.
The present study aims to elucidate the role for the CRF1 receptor in cognitive dysfunction and anxiety-like states induced by cocaine.
The genetic inactivation of the CRF1 receptor (CRF1+/- and CRF1-/-) does not influence recognition memory in drug-naïve mice, as assessed by the novel object recognition (NOR) test. Moreover, the chronic administration of escalating doses of cocaine (5-20 mg/kg, i.p.) induces NOR deficits, which are unaffected by CRF1 receptor-deficiency. However, the same drug regimen reveals an anxiety-like vulnerability to cocaine in CRF1-/- but not in wild-type or CRF1+/- mice, as assessed by the elevated plus maze test.
The present findings indicate dissociation of cognitive dysfunction and anxiety-like states induced by cocaine. Moreover, they unravel a novel mechanism of vulnerability to psychostimulant drugs.
摄入精神兴奋剂可能会导致认知功能障碍和负面情感样状态，并与应激反应系统活性增加有关。促肾上腺皮质释放因子 (CRF) 系统介导神经内分泌、行为和自主对应激源的反应，可能与物质相关障碍有关。CRF 信号由两种受体类型介导，命名为 CRF1 和 CRF2。
本研究旨在阐明 CRF1 受体在可卡因诱导的认知功能障碍和焦虑样状态中的作用。
CRF1 受体（CRF1+/- 和 CRF1-/-）的遗传失活不会影响药物-naive 小鼠的识别记忆，如通过新物体识别（NOR）测试评估。此外，递增剂量可卡因（5-20mg/kg，ip）的慢性给药会导致 NOR 缺陷，而 CRF1 受体缺失不会影响 NOR 缺陷。然而，相同的药物方案在 CRF1-/-而非野生型或 CRF1+/-小鼠中揭示了对可卡因的焦虑样易感性，如高架十字迷宫测试所示。
本研究结果表明可卡因诱导的认知功能障碍和焦虑样状态的分离。此外，它们揭示了对精神兴奋剂药物易感性的新机制。
