RESUMO
Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.
RESUMO
BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs with considerable morbidity and mortality. Immunomodulators for SJS/TEN including systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice. Emerging evidence suggested the therapeutic effects of tumor necrosis factor-α antagonists on SJS/TEN. OBJECTIVE: To compare the efficacy and safety of IVIG and systemic steroids in conjunction with or without etanercept, a tumor necrosis factor-α inhibitor, for patients with SJS/TEN. METHODS: We undertook a retrospective review of 41 patients with SJS/TEN admitted to our institution from 2015 to February 2021. A total of 25 patients with integrated data were involved in this study, of which 14 patients were treated with IVIG and corticosteroids and 11 were in addition given etanercept. The clinical characteristics, duration of hospitalization, exposure time to high-dose steroids, and the total amount of systemic steroids were analyzed. RESULTS: In comparison to conventional therapy, conjunction with etanercept reduced the duration of hospitalization (13.5 vs 19.0 days; P = .01), the exposure time of high-dose steroids (7.1 vs 14.9 days; P = .01), and the overall amount of systemic steroid (925 mg vs 1412.5 mg; P = .03) in patients with SJS/TEN. No pronounced adverse effects were observed within 6 months of follow-up after the treatment. CONCLUSION: The add-in of etanercept at the time of initiating conventional therapy could be a superior option to accelerate disease recovery and reduce the high dose and total amount of systemic steroids without pronounced adverse events in patients with SJS/TEN.