title: The antidepressant venlafaxine disrupts brain monoamine levels and neuroendocrine responses to stress in rainbow trout.
abstract: Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is a widely prescribed antidepressant drug routinely detected in the aquatic environment. However, little is known about its impact on the physiology of nontarget organisms. We tested the hypothesis that venlafaxine perturbs brain monoamine levels and disrupts molecular responses essential for stress coping and feeding activity in fish. Rainbow trout (Oncorhynchus mykiss) were exposed to waterborne venlafaxine (0.2 and 1.0 μg/L) for 7 days. This treatment elevated norepinephrine, serotonin, and dopamine levels in the brain in a region-specific manner. Venlafaxine also increased the transcript levels of genes involved in stress and appetite regulation, including corticotropin releasing factor, pro-opiomelanocortin B, and glucose transporter type 2 in distinct brain regions of trout. The drug treatment reduced the total feed consumed per day, but did not affect the feeding behavior of the dominant and subordinate fish. However, the subordinate fish from the venlafaxine-exposed group had significantly higher plasma cortisol levels compared to the subordinate fish in the control group. Collectively, our results demonstrate that venlafaxine, at environmentally realistic levels, is a neuroendocrine disruptor, impacting the stress and feeding responses in rainbow trout. We propose the midbrain region as a key target for venlafaxine impact and the mode of action involves abnormal monoamine content in trout.
authors.affiliation: Department of Biology, University of Waterloo , 200 University Avenue West, Waterloo, Ontario, Canada , N2L 3G1.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Melnyk-Lamont
authors.forename: Carol
authors.initials: C
authors.lastname: Best
authors.forename: Manuel
authors.initials: M
authors.lastname: Gesto
authors.forename: Mathilakath M
authors.initials: MM
authors.lastname: Vijayan
mesh_terms: D000378:Agonistic Behavior / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood; D009490:Neurosecretory Systems / Q000187:drug effects / Q000378:metabolism*; D017686:Oncorhynchus mykiss / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*; D000069470:Venlafaxine Hydrochloride / Q000009:adverse effects*
chemical_list: D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D001786:Blood Glucose; D012333:RNA, Messenger; D000069470:Venlafaxine Hydrochloride; D006854:Hydrocortisone