Neurotoxicology
-
Sex plays an important yet often underexplored role in neurodevelopment and neurotoxicity. While several studies report the importance of sex regarding anesthesia-induced neurotoxicity in neonatal mice, only few have focused on the late postnatal period. Here, to further understand the importance of sex regarding the neurobiological changes after early anesthesia during the critical synaptogenic period, we exposed postnatal day 16, 17 (PND 16, 17) mice to sevoflurane in pediatric patients and performed detailed evaluations in the hippocampus. ⋯ Exposure of mice to sevoflurane during the critical, late postnatal period induces sex-dependent changes in the hippocampus. Although often disregarded, our results confirm the importance of sex as a biological variable when studying the changes triggered by early anesthesia.
-
A new generation of novel cannabinoid compounds have been developed as marijuana substitutes to avoid drug control laws and cannabinoid blood tests. 5F-MDMB-PINACA (also known as 5F-ADB, 5F-ADB-PINACA), MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA (also known as FUB-AMB, MMB-FUBINACA) were tested for in vivo cannabinoid-like effects to assess their abuse liability. Locomotor activity in mice was tested to screen for locomotor depressant effects and to identify behaviorally-active dose ranges and times of peak effect. Discriminative stimulus effects were tested in rats trained to discriminate Δ9-tetrahydrocannabinol (3 mg/kg, 30-min pretreatment). 5F-MDMB-PINACA (ED50 = 1.1 mg/kg) and MDMB-CHIMICA (ED50 = 0.024 mg/kg) produced short-acting (30 min) depression of locomotor activity. ⋯ AMB-FUBINACA produced tremors at the highest dose tested. 5F-MDMB-PINACA (ED50 = 0.07), MDMB-CHIMICA (ED50 = 0.01 mg/kg), MDMB-FUBINACA (ED50 = 0.051 mg/kg), ADB-FUBINACA (ED50 = 0.075 mg/kg) and AMB-FUBINACA (ED50 = 0.029) fully substituted for the discriminative stimulus effects of Δ9-THC following 15-min pretreatment. All 5 compounds decreased locomotor activity and produced discriminative stimulus effects similar to those of Δ9-THC, which suggests they may have abuse liability similar to that of Δ9-THC. AMB-FUBINACA may have an increased risk of toxicities in recreational users.