Glucocorticoid receptor mediated the propofol self-administration by dopamine D1 receptor in nucleus accumbens

Abstract

Propofol, a widely used anesthetic, can cause addictive behaviors in both human and experimental animals. In the present study, we examined the involvement of glucocorticoid receptor (GR) signaling in the molecular process by which propofol may cause addiction. The propofol self-administration model was established by a fixed ratio 1 (FR1) schedule of reinforced dosing over successive 14days in rats. On day 15, the rats were treated with dexamethasone, a GR agonist (10-100μg/kg), or RU486, a GR antagonist (10-100μg/kg) at 1h prior to the last training. The animal behaviors were recorded automatically by the computer. The expression of dopamine D1 receptor in the nucleus accumbens (NAc) was examined by Western blot and the concentrations of plasma corticosterone were measured by enzyme-linked immunosorbent assay (ELISA). To further examine the specificity of GR in the process, mineralocorticoid receptor (MR) antagonist, spironolactone, and dexamethasone plus MR agonist, aldosterone, were also tested. Administration of dexamethasone (100μg/kg) or RU486 (⩾10mg/kg) significantly attenuated the rate of propofol maintained active nose-poke responses and infusions, which were accompanied by reductions in both plasma corticosterone level and the expression of D1 receptor in the NAc. Neither spironolactone alone nor dexamethasone combined with aldosterone affected the propofol-maintaining self-administrative behavior, indicating GR, but not MR, modulates the propofol reward in rats. In addition, neither the food-maintaining sucrose responses under FR1 schedule nor the locomotor activity was affected by any doses of dexamethasone or RU486 tested. These findings provide evidence that GR signaling may play an important role in propofol reward.

Presence of Inhibitory Glycinergic Transmission in Medium Spiny Neurons in the Nucleus Accumbens

“…Indeed, it was reported that D1 MSNs are important in the maintenance of propofol self-administration (Lian et al, 2013 ). Moreover, the systemic administration of a glucocorticoid receptor agonist in the nAc can regulate propofol self-administration behavior, altering the D1 receptor and c-Fos expression in rats (Wu et al, 2016 , 2018 ). Also, propofol increases DeltaFosB in nAc mediated by D1 receptors (Xiong et al, 2011 ) thus linking the rewarding effect of propofol directly to D1 MSNs.…”

Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects

“…Nevertheless, the fast onset of creating a short ecstatic and euphoric feeling, the capacity to induce sexual delusions, fantasies, and disinhibition, without many of the side effects that are associated with other drugs, and the fact of not being a controlled substance are the main reasons for its widespread abuse [ 158 , 160 ]. Pharmacodynamically, propofol increases dopamine concentrations in the nucleus accumbens , a phenomenon noted with other addictive psychoactive substances [ 161 – 164 ]. Chronic propofol abuse can result in tolerance, and repeated injections exceeding 100 times per day have been reported [ 163 , 165 ].…”

Effect of Dexmedetomidine-Mediated Insulin-Like Growth Factor 2 (IGF2) Signal Pathway on Immune Function and Invasion and Migration of Cancer Cells in Rats with Ovarian Cancer

“…Cell experiments further confirmed the positivity of DEX in reducing the invasion and migration of cancer cells in rats with ovarian cancer. One previous study confirmed that mifepristone and propofol have certain effects in anti-tumor therapy [30]. IN addition, Check et al found that propofol drugs could affect the biological behavior of breast cancer cells, and the right amount of propofol could reduce the invasion and migration of cancer cells [31].…”