The metabolic profiles of urine and blood plasma in drug-addicted rat models based on morphine (MOR), methamphetamine (MA), and cocaine (COC)-induced conditioned place preference (CPP) were investigated. Rewarding effects induced by each drug were assessed by use of the CPP model. A mass spectrometry (MS)-based metabolomics approach was applied to urine and plasma of MOR, MA, and COC-addicted rats. In total, 57 metabolites in plasma and 70 metabolites in urine were identified by gas chromatography-MS. The metabolomics approach revealed that amounts of some metabolites, including tricarboxylic acid cycle intermediates, significantly changed in the urine of MOR-addicted rats. This result indicated that disruption of energy metabolism is deeply relevant to MOR addiction. In addition, 3-hydroxybutyric acid, L-tryptophan, cystine, and n-propylamine levels were significantly changed in the plasma of MOR-addicted rats. Lactose, spermidine, and stearic acid levels were significantly changed in the urine of MA-addicted rats. Threonine, cystine, and spermidine levels were significantly increased in the plasma of COC-addicted rats. In conclusion, differences in the metabolic profiles were suggestive of different biological states of MOR, MA, and COC addiction; these may be attributed to the different actions of the drugs on the brain reward circuitry and the resulting adaptation. In addition, the results showed possibility of predict the extent of MOR addiction by metabolic profiling. This is the first study to apply metabolomics to CPP models of drug addiction, and we demonstrated that metabolomics can be a multilateral approach to investigating the mechanism of drug addiction.
Autism spectrum disorder (ASD) is a multifactorial disorder with characteristic synaptic and gene expression changes. Early intervention during childhood is thought to benefit prognosis. Here, we examined the changes in cortical synaptogenesis, synaptic function, and gene expression from birth to the juvenile stage in a marmoset model of ASD induced by valproic acid (VPA) treatment. Early postnatally, synaptogenesis was reduced in this model, while juvenile-age VPA-treated marmosets showed increased synaptogenesis, similar to observations in human tissue. During infancy, synaptic plasticity transiently increased and was associated with altered vocalization. Synaptogenesis-related genes were downregulated early postnatally. At three months of age, the differentially expressed genes were associated with circuit remodeling, similar to the expression changes observed in humans. In summary, we provide a functional and molecular characterization of a non-human primate model of ASD, highlighting its similarity to features observed in human ASD.
Traditionally, safety evaluation at the early stage of drug discovery research has been
done using
in silico
,
in vitro
, and
in
vivo
systems in this order because of limitations on the amount of compounds
available and the throughput ability of the assay systems. While these
in
vitro
assays are very effective tools for detecting particular tissue-specific
toxicity phenotypes, it is difficult to detect toxicity based on complex mechanisms
involving multiple organs and tissues. Therefore, the development of novel high throughput
in vivo
evaluation systems has been expected for a long time. The
zebrafish (
Danio rerio
) is a vertebrate with many attractive
characteristics for use in drug discovery, such as a small size, transparency, gene and
protein similarity with mammals (80% or more), and ease of genetic modification to
establish human disease models. Actually, in recent years, the zebrafish has attracted
interest as a novel experimental animal. In this article, the author summarized the
features of zebrafish that make it a suitable laboratory animal, and introduced and
discussed the applications of zebrafish to preclinical toxicity testing, including
evaluations of teratogenicity, hepatotoxicity, and nephrotoxicity based on morphological
findings, evaluation of cardiotoxicity using functional endpoints, and assessment of
seizure and drug abuse liability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.