Tuesday, March 11, 2014

Effect of Cyanide and Sodium azide on fish surfacing reaction

Weiss and colleagues tested the hypothesis that LSD acts by anoxia and asphyxia. They added Siamese fighting fish to water containing the oxidase inhibitors, potassium cyanide (KCN) and sodium azide. KCN and sodium azide affected Siamese fighting fish in a way which was very similar to LSD, suggesting that LSD might normally work by preventing oxygen uptake. Figure 2 (below) shows the fish surfacing reaction for 1 ug LSD (left) and 1 ug KCN (middle). There is no surfacing reaction in the H2O control (right).


It was interesting that KCN was nearly as potent as LSD, since there are few drugs, with the exception of other hallucinogens and microtubule toxins, that cause LSD-like behavior in the same concentration range as LSD. However it was noted that since the molecular weight of LSD-25 is five times that of KCN, then more KCN molecules are needed to produce the effect than LSD molecules in a biological assay.

There were some differences between KCN and LSD, for example the gills were more inflamed with KCN treatment. If fish are transferred to fresh water, they recovered more quickly from 1 ug/mL KCN than 1 ug/mL LSD. The figure below shows the KCN surfacing reaction in juvenile Betta fish. Doses of KCN at 1.2 ug/mL (solid circles), 0.6 ug/mL (open circles), and 0.3 ug/mL (half-filled circles) are plotted on the LSD surfacing curve (smoothed lines) for reference.


The authors observed that CO2 poisoning itself causes a nose up-tail down reaction in fish. When carbon dioxide was permitted to accumulate in the absence of renewed oxygen, all of the fish assumed the nose up-tail down position in several hours. Thus inhibition of O2 oxidation was a general feature of the intoxication produced by LSD, KCN, and sodium azide.
"A decreased oxygen supply with simultaneous prevention of accumulation of carbon dioxide resulted in the nose up-tail down position similar to that for LSD in several hours, the fish remaining alive." (Weiss,B. 1958)

A concentration of 100 ug/mL methylene blue also caused a nose up-tail down reaction. There were similar results with gentian violet and Bindschedler's green.



Reference

WEISS B., H. A. ABRAMSON and M. O. BARON (1958). Lysergic acid diethylamide (LSD-25). XXV. Effect of potassium cyanide and other oxidase and respiratory inhibitors on the Siamese fighting fish. A.M.A. Archives of Neurology and Psychiatry 80, 345-350.