Heroin and cocaine are both highly addictive drugs that cause unique physiological and behavioral effects. These drugs are often co-administered and cocaine has been found in ~20% of cases of opioid overdose death. Respiratory depression followed by brain hypoxia is the most dangerous effect of high-dose opioids that could result in coma and even death. Conversely, cocaine at optimal self-administering doses increases brain oxygen levels. Considering these differences, it is unclear what pattern of oxygen changes will occur when these drugs are co-administered. Here, we used high-speed amperometry with oxygen sensors to examine changes in oxygen concentrations in the nucleus accumbens (NAc) induced by intravenous (iv) cocaine, heroin, and their mixtures in freely-moving rats. Cocaine delivered at a range of doses, both below (0.25 mg/kg) and within the optimal range of self-administration (0.5 and 1.0 mg/kg) modestly increased NAc oxygen levels. In contrast, heroin increased oxygen levels at a low reinforcing dose (0.05 mg/kg), but induced a biphasic down-up change at higher reinforcing doses (0.1 and 0.2 mg/kg), and caused a strong monophasic oxygen decrease during overdose (0.6 mg/kg). When combined at moderate doses, cocaine (0.25, 0.5 mg/kg) slightly increased and prolonged oxygen increases induced by heroin alone (0.5 and 0.1 mg/kg), but oxygen decreases were identical when cocaine (1 mg/kg) was combined with heroin at large doses (0.2 and 0.6 mg/kg). Therefore, health dangers of speedball may result from de-compensation of vital functions due to diminished intra-brain oxygen inflow induced by high-dose heroin coupled with enhanced oxygen use induced by cocaine.

海洛因和可卡因都是高度成瘾的药物，会导致独特的生理和行为影响。这些药物通常是共同给药的，在约 20% 的阿片类药物过量死亡病例中发现了可卡因。呼吸抑制和脑缺氧是高剂量阿片类药物最危险的影响，可能导致昏迷甚至死亡。相反，最佳自我给药剂量的可卡因会增加脑氧水平。考虑到这些差异，尚不清楚当这些药物共同给药时会发生什么样的氧变化模式。在这里，我们使用带有氧传感器的高速电流测定法来检查由静脉注射 (iv) 可卡因、海洛因及其混合物在自由移动的大鼠中引起的伏隔核 (NAc) 中氧浓度的变化。可卡因以一系列剂量递送，均低于 (0. 25 毫克/公斤）和自我给药的最佳范围（0.5 和 1.0 毫克/公斤）适度增加 NAc 氧水平。相比之下，海洛因在低强化剂量（0.05 mg/kg）下增加氧气水平，但在较高强化剂量（0.1 和 0.2 mg/kg）下引起双相向下变化，并在过量期间引起强烈的单相氧减少。 0.6 毫克/公斤）。当以中等剂量联合使用时，单独使用海洛因（0.5 和 0.1 毫克/千克）引起的可卡因（0.25、0.5 毫克/千克）轻微增加和氧气增加时间延长，但当可卡因（1 毫克/千克）与可卡因（1 毫克/千克）联合使用时，氧气减少量相同大剂量海洛因（0.2 和 0.6 毫克/公斤）。因此，由于高剂量海洛因引起的脑内氧气流入减少，再加上可卡因引起的氧气使用增加，因此速度球的健康危害可能是由于生命功能的代偿失调造成的。