The Role of NMDA receptors in rat propofol self-administration [post]

2020 unpublished
Aim 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 of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration. Methods Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training,
more » ... y). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more 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. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited 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), with increased locomotor activity (F(3, 20)=22.812, P<0.01). Conclusion These findings indicate that NMDA receptors may play a role in regulating rat selfadministration of propofol. Background Propofol (2, is an anesthetic agent that has the potential for recreational abuse, as its intake is associated with pleasant and euphoric feelings[1]. Indeed, one anesthesiologist that had been self-administering propofol reported eventual propofol-dependence [2] . Both conditioned place preference and self-administration studies in animals have further confirmed that propofol can Thanks to the professor Qing-quan Lian for his guidance on this paper Author information Affiliations
doi:10.21203/rs.2.23365/v2 fatcat:5kksrruruzghbatelwhjoaswcq