Cocaine profoundly affects both cerebral blood vessels and neuronal activity in the brain. The vasoconstrictive effects of cocaine, concurrently with its effects on neuronal [Ca²⁺]_i accumulation are likely to jeopardize neuronal tissue that in the prefrontal cortex (PFC) could contribute to impaired self-regulation and compulsive cocaine consumption. Here we used optical imaging to study the cerebrovascular and neuronal effects of acute cocaine (1 mg/kg i.v.) and to examine whether selective blockade of L-type Ca²⁺ channels by Nifedipine (NIF) (0.5 mg/kg i.v.) would alleviate cocaine’s effects on hemodynamics (measured with cerebral blood volume, HbT), oxygenation (measured with oxygenated hemoglobin, HbO₂) and neuronal [Ca²⁺]_i, which were concomitantly measured in the PFC of naive rats. Our results show that in the PFC acute cocaine significantly reduced flow delivery (HbT), increased neuronal [Ca²⁺]_i accumulation and profoundly reduced tissue oxygenation (HbO₂) and these effects were significantly attenuated by NIF pretreatment. They also show that cocaine-induced vasoconstriction is distinct from its increase of neuronal [Ca²⁺]_i accumulation though both of them contribute to hypoxemia and both effects were attenuated by NIF. These results provide evidence that blockade of voltage-gated L-type Ca²⁺ channels might be beneficial in preventing vasoconstriction and neurotoxic effects of cocaine and give support for further clinical investigations to determine their value in reducing cocaine’s neurotoxicity in cocaine use disorders.

可卡因深刻地影响脑血管和大脑中的神经元活动。可卡因的血管收缩作用及其对神经元 [Ca ²⁺ ] _i积累的影响可能会危害前额叶皮层 (PFC) 中的神经元组织，从而导致自我调节受损和强迫性可卡因消耗。在这里，我们使用光学成像研究急性可卡因 (1 mg/kg iv) 对脑血管和神经元的影响，并检查硝苯地平 (NIF) (0.5 mg/kg iv)对 L 型 Ca ²⁺通道的选择性阻断是否会缓解可卡因对血液动力学（用脑血容量 HbT 测量）、氧合作用（用氧合血红蛋白 HbO ₂测量）和神经元 [Ca²⁺ ] _i，这是在幼稚大鼠的 PFC 中同时测量的。我们的结果表明，在 PFC 急性可卡因中，流量输送 (HbT) 显着减少，神经元 [Ca ²⁺ ] _i积累增加，组织氧合 (HbO ₂ ) 显着减少，并且 NIF 预处理显着减弱了这些影响。他们还表明，可卡因诱导的血管收缩与其神经元 [Ca ²⁺ ] _i积累的增加不同，尽管它们都会导致低氧血症并且这两种作用都被 NIF 减弱。这些结果提供了电压门控 L 型 Ca ^{2+阻断的证据}通道可能有利于预防可卡因的血管收缩和神经毒性作用，并支持进一步的临床研究以确定它们在减少可卡因使用障碍中可卡因的神经毒性方面的价值。