Ming Xiong1, Jingyuan Li, Jiang H Ye, Chunxiang Zhang. 1. Department of Anesthesiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07101, USA.
Abstract
BACKGROUND: It is well established that all drugs of abuse converge onto common circuitry and induce chronic addiction by modulating the addictive signaling molecules such as DeltaFosB in the mesocorticolimbic system. Recent case reports suggest that propofol may have abuse potential. However, there is no direct evidence showing that propofol has an effect on the key addictive signaling molecules in the mesocorticolimbic system. In this study, we determined the effect of propofol on the expression of DeltaFosB in rat nucleus accumbens (NAc) and the potential mechanism involved. METHODS: To determine the effect of propofol on the expression of DeltaFosB in rat NAc, 2 well-known addictive agents, ethanol and nicotine, were used as positive controls. Experiments were conducted on 36 male Sprague-Dawley rats (150 to 200 g). These animals were divided into 4 treatment groups: vehicle (saline), propofol (10 mg/kg), ethanol (1 g/kg), and nicotine (0.5 mg/kg). All drugs were administered by intraperitoneal injection twice per day for 7 days. The animals were then killed and their NAc were isolated for DeltaFosB measurements. RESULTS: As expected, both ethanol and nicotine significantly increased DeltaFosB expression. Intriguingly, propofol elicited a robust increase in DeltaFosB expression similar to that of ethanol and nicotine. Moreover, the dopamine receptor D1, an upstream molecule of DeltaFosB, was also significantly upregulated by propofol. CONCLUSIONS: In the current study, we have identified, for the first time, that propofol is able to induce the addictive signaling molecule DeltaFosB in NAc via dopamine receptor D1. This new evidence at the molecular level suggests that propofol may have abuse potential.
BACKGROUND: It is well established that all drugs of abuse converge onto common circuitry and induce chronic addiction by modulating the addictive signaling molecules such as DeltaFosB in the mesocorticolimbic system. Recent case reports suggest that propofol may have abuse potential. However, there is no direct evidence showing that propofol has an effect on the key addictive signaling molecules in the mesocorticolimbic system. In this study, we determined the effect of propofol on the expression of DeltaFosB in rat nucleus accumbens (NAc) and the potential mechanism involved. METHODS: To determine the effect of propofol on the expression of DeltaFosB in rat NAc, 2 well-known addictive agents, ethanol and nicotine, were used as positive controls. Experiments were conducted on 36 male Sprague-Dawley rats (150 to 200 g). These animals were divided into 4 treatment groups: vehicle (saline), propofol (10 mg/kg), ethanol (1 g/kg), and nicotine (0.5 mg/kg). All drugs were administered by intraperitoneal injection twice per day for 7 days. The animals were then killed and their NAc were isolated for DeltaFosB measurements. RESULTS: As expected, both ethanol and nicotine significantly increased DeltaFosB expression. Intriguingly, propofol elicited a robust increase in DeltaFosB expression similar to that of ethanol and nicotine. Moreover, the dopamine receptor D1, an upstream molecule of DeltaFosB, was also significantly upregulated by propofol. CONCLUSIONS: In the current study, we have identified, for the first time, that propofol is able to induce the addictive signaling molecule DeltaFosB in NAc via dopamine receptor D1. This new evidence at the molecular level suggests that propofol may have abuse potential.
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