The role of NMDA receptors in rat propofol self-administration.

BACKGROUND: Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration. METHODS: Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, followed 10 min later by a propofol self-administration session. RESULTS: After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P < 0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P < 0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P > 0.05) or inactive (F (3, 28) = 0.047, P > 0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P = 0.006, P < 0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F (3, 20) = 20.8673, P < 0.01) and the number of sucrose pellets (F (3, 20) = 23.77, P < 0.01), while their locomotor activity was increased (F (3, 20) = 22.812, P < 0.01). CONCLUSION: These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

Dexmedetomidine inhibits apoptosis and expression of COX-2 induced by lipopolysaccharide in primary human alveolar epithelial type 2 cells.

Alveolar epithelial type II cells (ATII cells) are the main target cells being damaged and releasing the inflammatory mediators during acute respiratory distress syndrome (ARDS). Extensive apoptosis of epithelial cells leads to the breakdown of the alveolar-epithelial barrier in ARDS. Cyclooxygenase-2 (COX-2) plays an important role in pulmonary inflammatory response. Dexmedetomidine (DEX), a potent selective α2 adrenergic receptor (α2-AR) agonist, presents sedative, anxiolytic, and analgesic effects for anesthetic procedures. DEX has anti-apoptotic and anti-inflammatory properties. Our study demonstrated that DEX exerted anti-apoptotic effect on primary human epithelial cells with the inhibition of caspase activation, which was partly via the α2AR/PI3K/AKT pathway. Moreover, DEX significantly reduced the expression of COX-2 as well as prostaglandinE2 (PGE2) and tumor necrosis factor-α (TNF-α) production induced by lipopolysaccharide (LPS). Our next step is to determine whether DEX can regulate apoptosis in animal models. These results suggest DEX may be a promising therapy for preventing and treating ARDS as well as chronic diseases by directly targeting epithelial cell actions.