Toads are remarkable creatures, and pet owners the world over can tell you what a terrible thing it is when a dog or cat consumes one.  Toads, you see, have sophisticated defense mechanisms that go well beyond taking giant leaps away from their predators.  They secrete what we call bufotoxins that can cause anything from convulsions to death among canids, although this has not stopped dogs or humans from licking toads to get high.

Note: That is about as dumb a thing as you can do. Paralysis and death are some very real outcomes of toad licking. Despite this high-end security system, toads do in fact get eaten quite often.  Their primary predators are snakes, many of whom subsist almost entirely on toads and are termed bufophagous snakes (or toad-eating snakes, after the common genus of toad Bufo). So what’s their secret? Why do only some snakes eat toads while others desist?

Why don’t bufophagous snakes suffer paralysis and death? It turns out, it isn’t as simple as calling them “immune” to the toxins produced by toads.

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Bufotoxins are secreted by the parotoid glands in the skin of many toads and salamanders, located on the back and shoulders of the animal. They are contained in a solution of venom that has many ingredients, including 5-MeO-DMT, a psychedelic tryptamine, that has lent these toads the moniker ‘psychoactive.’  This has, of course, proved inspiration for all kinds of ill-advised toad-related behaviours among humans. And some cartoon depictions.

Bufo alvarius, a psychoactive toad, with large parotoid glands on its shoulders.

When an animal ingests a bufotoxin, the toxin migrates to the heart and disables sodium-potassium pumps (or Na+, K+-ATPases; NKAs) that are critical to generating contractions.  When these ion pumps have toxins bound to them, they result in cardiac arrhythmias, not because the heart cannot pump blood, but because the toxin increases the contractile strength of the heart muscles. NKA dysfunction can then result in cardiac failure and death.

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Early suggestions that some bufophagous snakes displayed large size differences between the sexes in adrenal glands led researchers to evaluate this trait in a variety of snakes. First, they chose four pairs of distantly related snakes, with each pair containing one species of toad-eating snake and one that does not ingest toads.  Then, they scoured museums for specimens of these snakes, and carefully dissected out the adrenal glands of both male and female snakes. Their results were both enlightening and puzzling.

Hypsiglena species, a nonbufophagous snake                                 Photo by randomtruth on Flickr
Heterodon platirhinos, the eastern hognose snake, which is bufophagous                                                                                  Photo from Wikimedia Commons

The most straightforward outcome that the researchers could have anticipated was an increase in adrenal gland size among toad-eating snakes.  The adrenal gland produces hormones that maintain elevated concentrations of NKAs, which come in handy during the digestion of bufotoxins.  However, their results were a little more complicated.

They discovered that all toad-eating snakes did not have enlarged adrenal glands; intriguingly, only the males did! All non-bufophagous snakes of both sexes displayed no such dimorphism in adrenal gland size.  It appears that while adrenal glands surely have something to do with granting snakes a tolerance for bufotoxins, there is more to this story than meets the eye.

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This sex-biased change in adrenal gland sizes was found to exist in newly hatched, yet unfed, infant snakes of the eastern hog-nosed snake (Heterodon platirhinos), implying that dietary intake after birth does not create enlarged glands in males. However, when embryos of the toad-eating, tiger keelback snake (Rhabdophis tigrinus) were exposed to bufotoxins, they subsequently hatched into little, toad-venom resistant snakes. This demonstrates that the environment in utero could have something to do with venom resistance in snakes. An investigation of these factors in the same snake species might be more revealing.

Just as exposure to mercury while in the womb can cause birth defects in humans, amphibians and reptiles have also shown that environmental contaminants can be transferred by a mother to her embryos.  Thus, this early exposure to bufotxins in the mother’s own diet could result in enlarged adrenal glands in young snakes.  (However, this does not explain sexual dimorphism at birth in adrenal gland sizes). Females themselves will have less of the neurotoxin in their systems, since some of it would now be within their eggs.  An overall lower level of bufotoxin can be expected in females than males, which in turn could explain why females do not require enlarged adrenal glands to counter the toxins – they just have less of it that needs to be detoxified!

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One rather unique exception to this general pattern is Natrix natrix, a non-venomous (to us) grass snake from Europe.  Although it subsists on the common toad (Bufo bufo) that definitely produces bufotoxins, it does not appear to have any adrenal gland sexual dimorphism.  In fact, one study even showed that female grass snakes eat more toads than do males.  The specimens that were dissected were collected from across Europe, excluding location-bias as an explanation for this outcome. In short, it’s a good old-fashioned mystery!

Sources:

Mohammadi S., McCoy K.A., Hutchinson D.A., Gauthier D.T. & Savitzky A.H. (2013). Independently evolved toad-eating snakes exhibit sexually dimorphic enlargement of adrenal glands, Journal of Zoology, n/a-n/a. DOI:

More on toads and snakes:

Some information on psychoactive toads from people who specialise in all things psychoactive:)

What happens when you take aphrodisiacs that you don’t know the contents of – toad venom can mimic digitalis poisoning.

Descriptions of the experience of ingesting toad venom – my strong suggestion is to avoid this, for the sake of the toad and yourself.

Trippy! The tiger keelback actually uses the toxins it ingests from toads to make itself poisonous to other animals. This is a la Ed Yong

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