Biodistribution, cardiac and neurobehavioral assessments, and neurotransmitter quantification in juvenile rats following oral administration of aluminum oxide nanoparticles.

Little is known about the uptake, biodistribution, and biological responses of nanoparticles (NPs) and their toxicity in developing animals. Here, male and female juvenile Sprague-Dawley rats received four consecutive daily doses of 10 mg/kg Al2 O3 NP (diameter: 24 nm [transmission electron microscope], hydrodynamic diameter: 148 nm) or vehicle control (water) by gavage between postnatal days (PNDs) 17-20. Basic neurobehavioral and cardiac assessments were performed on PND 20. Animals were sacrificed on PND 21, and selected tissues were collected, weighed, and processed for histopathology or neurotransmitter analysis. The biodistribution of Al2 O3 NP in tissue sections of the intestine, liver, spleen, kidney, and lymph nodes were evaluated using enhanced dark-field microscopy (EDM) and hyperspectral imaging (HSI). Liver-to-body weight ratio was significantly increased for male pups administered Al2 O3 NP compared with control. HSI suggested that Al2 O3 NP was more abundant in the duodenum and ileum tissue of the female pups compared with the male pups, whereas the abundance of NP was similar for males and females in the other tissues. The abundance of NP was higher in the liver compared with spleen, lymph nodes, and kidney. Homovanillic acid and norepinephrine concentrations in brain were significantly decreased following Al2 O3 NP administration in female and male pups, whereas 5-hydroxyindoleacetic acid was significantly increased in male pups. EDM/HSI indicates intestinal uptake of Al2 O3 NP following oral administration. Al2 O3 NP altered neurotransmitter/metabolite concentrations in juvenile rats' brain tissues. Together, these data suggest that orally administered Al2 O3 NP interferes with the brain biochemistry in both female and male pups.

Synthetic cathinone self-administration in female rats modulates neurotransmitter levels in addiction-related brain regions.

Synthetic cathinones are used for their stimulant-like properties. Stimulant-induced neurochemical changes are thought to occur at different times in different brain regions and neurotransmitter systems. This study sought to examine the behavioral and neurochemical effects of α-pyrrolidinopentiophenone (α-PVP) and mephedrone (4MMC) in female rats. Methods probed the chronology of effects of synthetic cathinone exposure. Female rats were trained to self-administer α-PVP, 4MMC, or saline. Drug exposure ceased after 7 days of autoshaping for half of each drug group; the other half self-administered for another 21 days. Amygdala, hippocampus, hypothalamus, PFC, striatum, and thalamus were extracted, and tissue was analyzed with electrochemical detection and liquid chromatography mass spectrometry. Responding was minimal during autoshaping; thus, most infusions were delivered noncontingently in the autoshaping phase. Rats acquired self-administration of α-PVP and 4MMC. Synthetic cathinone administration, and duration of exposure produced several effects on neurotransmitters. α-PVP primarily increased serotonin, 5-hydroxy-3-acetic acid (5-HIAA), norepinephrine, and glutamate in hypothalamus. In contrast, 4MMC decreased serotonin and 5-HIAA in several brain regions. Longer durations of exposure to both synthetic cathinones increased 5-HIAA, norepinephrine, and glutamate in multiple brain regions compared to the short exposure during autoshaping. Notably, both α-PVP and 4MMC produced minimal changes in dopamine levels, suggesting that the dopaminergic effects of these synthetic cathinones are transient. These alterations in neurotransmitter levels indicate that synthetic cathinone use may produce differential neurochemical changes during the transition from use to abuse.