Evidence of histamine receptors in fish brain using an in vivo [14C]2-deoxyglucose autoradiographic method and an in vitro receptor-binding autoradiographic method.

It was hypothesized that fish possess functioning H1 histamine receptors that have the ability to bind agonists and antagonists specific to the H1 histamine receptor subtype. For these experiments, a combination of a novel, in vivo 2-deoxyglucose method and a standard in vitro autoradiography procedure was utilized. A regional, statistically significant dose response in neurological functioning was observed when fish were exposed to histaminergic agents (i.e., H1 agonists and antagonists), which created the first neurological profile for the H1 histamine receptor in fish brain. The H1 histamine receptor was chosen as a characterization receptor in fish because histamine has been linked to a variety of neurological functions such as the control of arousal, attention, sensory processing, and cognition. Histamine also plays a role in pituitary hormone secretion, appetite control, and, potentially, regulation of vestigular reactivity. In addition, the fish brain is well characterized structurally, and the existence of an H3-like receptor has been documented recently in zebrafish. However, to date there is little detailed information about specific localization and functioning of the H1 histamine receptor in fish.

The N-methyl-D-aspartate neurotransmitter receptor is a mammalian brain target for the dinoflagellate Pfiesteria piscicida toxin.

Blooms of Pfiesteria piscicida, a dinoflagellate in eastern U.S. coastal rivers, are believed to secrete toxins that kill fish and produce short-term memory loss in humans. Only one or two of Pfiesteria's multiple stages secrete the toxin, and only under certain environmental conditions. Thus, neither the presence of Pfiesteria nor fish kill alone can be indicative of toxin presence. The objective of this study was to identify the mammalian molecular brain target for the toxin that is associated with decrements in memory. Seven rat brain neurotransmitter receptors were selected to study because of their reported roles in cognitive function: receptors for nicotine, muscarine, AMPA/kainate, N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid, and dopamine 1 and 2. The effects of 17 environmental and laboratory samples on radioactive ligand binding to these receptors were studied. Of the seven receptors, binding only to the NMDA receptor was inhibited by only the two Pfiesteria-containing waters (identified by PCR) that also killed fish, and not by any of the other 15 samples tested. It is suggested that inhibition of NMDA-receptor binding is the cause of memory loss in exposed humans. Thus, it could be a useful biomarker for the toxin's presence in rivers for decisions on closures and for identification of the fractions containing the toxin during its purification. Knowledge of the toxin's molecular target, and how it affects its function, also leads to suggestions for therapeutics to use in animal models.