4-Nonylphenol and 4-tert-octylphenol induce anxiety-related behaviors through alternation of 5-HT receptors and transporters in the prefrontal cortex
Environmental endocrine disruptors 4-nonylphenol (NP) and 4-tert-octylphenol (OP) may cast huge harm to human health. We used a rat model to observe the influence of NP or/and OP exposure on anxiety-related behaviors and the underlying mechanisms. Eighty male Sprague-Dawley (SD) rats were randomly divided into 10 groups: control group (corn oil), NP groups [30, 90, 270 mg/kg], OP groups [40, 120, 360 mg/kg] and NO groups [(mixed with the corresponding NP, OP alone exposed low, medium and high dose according to the natural environment exists NP:OP = 4:1]. The rats were orally administered every other day for 30 days. The neurobehaviors of rats were evaluated by open-field test (OFT) and elevated plus-maze test (EPM), and the concentrations of 5-HT, monoamine oxidase (MAOA), serotonin transporter (SERT), vesicular monoamine transporter 2 (VAMT2), 5-hydroxytryptamine 1A (5-HT 1A ), 5-hydroxytryptamine 2A (5-HT 2A )，and 5-hydroxytryptamine 2C (5-HT 2C ) in the rat prefrontal cortex were analyzed by ELISA . OFT and EPM tests showed that NP or/and OP exposure induced anxiety-related behaviors in rats. 5-HT levels were significantly increased compared with the control group. The levels of MAOA, SERT, VAMT2, 5-HT 1A , 5-HT 2A, and 5-HT 2C in the prefrontal cortex reduced in different degrees by high-doses NP or/and OP exposure. In summary, NP or/and OP exposure might cause anxiety-related behaviors in rats through regulating neurotransmitter 5-HT levels by altering the expression of 5-HT decomposition enzyme MAOA, transporters SERT and VMAT2, and 5-HT receptors 5-HT 1A , 5-HT 2A, and 5-HT 2C .
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