Sweirzbinski M. E., Lazarchik A. R., and Herberholz J. Prior social experience affects the behavioral and neural responses to acute alcohol in juvenile crayfish. Journal of Experimental Biology (2017). Doi: 10.1242/jeb.154419.
Buzzed. Tipsy. Wasted. Belligerent. Paranoid. These are a few of my favorite drunks. A bit (or more) of grog is a popular remedy for those looking to loosen up at the end (or beginning) of a long day. And, a lot of people drink. According to a 2015 survey conducted by the United States National Institutes of Health nearly ninety percent of adults in the United States report having drunk at some point in their lives, while over half of the respondents reported that they had something to drink in the last month. Therefore, it might come as a surprise that scientists have very little idea of how humanity’s favorite poison perturbs the brain and nervous system.
Ethical dilemmas aside, directly studying the effects of alcohol on human subjects is about as challenging as, well, herding a bunch of drunks. Hence, scientists turn to animal models to study the causes and effects of intoxication. While mammalian models such as apes and mice might seem like the most logical choices for studying the mechanisms of intoxication, the nervous systems of these vertebrates are just about as poorly understood as our own. Meanwhile, on another of branch of the evolutionary tree of life, our invertebrate ancestors have far simpler nervous systems that can still lend insights into the workings of their more complex counterparts.
In people drunkenness usually follows a trajectory from increased activity (decreased inhibition, euphoria, belligerence, paranoia) after the first few drinks, to loss of motor function (slurred speech, stumbling, blackout) following a few too many. Moreover, the number of drinks that it takes one to reach that happy (or unhappy) place varies. To an extent this variation has to do with how we metabolize alcohol, which is affected by things like conditioning to alcohol, body mass index, the presence or absence of genetically inherited traits that impair the body’s ability to metabolize (i.e. breakdown) alcohol, and whether we have had something to eat before indulging in drink. All of the above have to do with the how our bodies metabolize alcohol, but metabolism is only part of the story when it comes to alcohol tolerance. Another factor seems to depend on social conditioning (i.e. social status and social life). While the social isolation that results from alcoholism could be a two-way street (i.e., which came first the isolation or the alcoholism?), studies on mammals have suggested that social isolation leads to increased tolerance to alcohol possibly due to a decrease in the number of receptors that interact with alcohol in the brain, hence numbing the system to the drug. In crayfish it has been shown that those deprived of social contact tend to be more likely to seek a high. Like much of our understanding of the mechanisms that underlie the effects of alcohol, the role of social history (and status) on alcohol tolerance is not well understood. In a recent study reported in the journal Experimental Biology, a team of scientists from the University of Maryland lead by Matthew Swierzbinski has provided the first link between social history and alcohol tolerance at the level of the nervous system in drunk crawdads (mini freshwater-dwelling lobsters). These findings suggest that physical change in the crawdad’s brains resulting from past periods of social isolation lead to increased tolerance to alcohol.
The effects of drugs on behavior in crayfish seems to mirror those observed humans. Hence, crayfish have long been used as addiction models for studying a diverse array of substances such as amphetamines, cocaine, and alcohol. In the case of alcohol, crayfish experience drunkenness in a similar manner to humans and at comparable blood alcohol levels. What’s more, like humans, they develop tolerance to alcohol as a result of exposure. Piggy-backing off of these earlier studies on crayfish, Swierzbinski and colleagues set out to tackle investigate the effect of social history on alcohol tolerance in crayfish.
When crawdad’s get drunk they exhibit two unambiguous behaviors. The first is behavior is a characteristic flopping of the tail, which occurs as a result of medium alcohol exposure—a buzz, if you will. In a more advanced state of inebriation, crawdad’s have the habit of rolling onto their backs, apparently unable to right themselves. To study these behaviors, Swierzbinski and colleagues monitored crayfish placed in alcohol baths by video, and determined the onset and number of times each drunken behavior was observed over a period of an hour or two.
To get a sense of the crayfish’s alcohol tolerance, the researchers examined their behavior in three different concentrations of alcohol. The highest concentration was equivalent to the alcohol content of a beer, the second half that, and the lowest concentration came close to a kombucha. In the most potent treatment, tail-flipping occurred on average 20 minutes after the start of the bath, and about double that time in medium treatment, and a little over twice that in the lowest treatment. Similarly, the onset of the more advanced drunkenness (i.e. the rollover) was observed an average of thirty-five minutes after exposure for the highest concentration, and twice that for the medium. Interestingly nine out of the fifteen individuals subjected to the lowest alcohol concentration exhibited no tail flipping over the three-hour duration of the experiment, while only three of the fifteen adopted the rolled over position at that concentration. In other words, not all crayfish exhibited the same alcohol tolerance.
Having demonstrated the basal alcohol tolerance of the crayfish, the researchers began to explore the effects of social history on variability in alcohol tolerance. They now subjected a cohort of crayfish to solitary confinement to simulate the effect of social isolation. Nineteen individuals of comparable size were chosen to either subside in the party tank, or to swim solo for a week. Following the de-socialization period, the crayfish were treated to a well-deserved beer bath. Excitingly, the researchers observed a ten-minute delay in the onset of tail-flipping for the isolated population with respect to their communal counterparts who never knew loneliness. Despite the fact these crayfish had been reared communally in the company of fifty to one hundred siblings, the period of isolation left its mark with an apparent increase in alcohol tolerance.
Now that the researchers had pinned down the social effects of alcohol consumption, they wanted to dig a little bit deeper and look at what the underlying cause might be for the change in alcohol tolerance. Based on the prior study of the nerves involved in triggering the tail-flipping behavior in crayfish, the researchers chose to investigate the relationship of the “excitation potential”, the threshold electrical electrical charge required elicit the response of tail-flipping, and alcohol tolerance in socialized versus de-socialized crayfish. To do this they inserted wires into the abdomens of cohorts of eleven socialized and de-socialized crayfish in ‘beer’ baths that allowed to deliver an electrical shock to their nervous systems. The animals were subjected to shocks below and above the threshold potential in intervals of two minutes over the course of two hours. In order to ensure that any changes observed were due to the alcohol treatment, and not due to the repeated pulsing, the crayfish were only exposed to alcohol during the second hour of pulsing. Correspondingly, the changes excitation potential observed for both groups of animals were not substantially altered in the first hour. However, during the hour in which the crayfish were wallowing in alcohol, the researchers observed a reduction in threshold potential for both groups. However, that reduction occurred more quickly, and was much more pronounced in the socialized animals in comparison to their ex-compatriots. Hence, the result at the level of the nervous system mirrored the observed behavioral differences in social versus isolated animals.
Having shown that the effects of social history could be translated to the level of the nervous system, Swierzbinski and colleagues next aimed to show that their observations could be attributed to a single neuron cell by inserting electrodes with surgical precision in the lateral giant interneuron, the central nerve the controls abdominal motion in invertebrates like crayfish. This time the crayfish were pinned down in petri dish (i.e. not allowed to swim freely). Rather than placing the specimens in an alcohol bath, the nerve cells were directly infused with low and high concentrations of alcohol chosen to mimic the anticipated internal alcohol levels of animals exposed to kambucha-like and beer-like levels of alcohol, respectively. They next pulsed an electrical voltage slightly below the threshold required to elicit tail-flipping in sober animals. For the lower alcohol concentration, the results at the single neuron level again mirrored the system-level experiment, with just under eighty percent of socialized animals brought to threshold in contrast to a little over half of the de-socialized animals following suit.
Lastly, the researchers wanted to know whether the change in nerve cells was due to a local effect on the cells themselves, or whether the effect occurred as a result of changes to the brain. Hence, they detached the tails from the crayfish, and repeated the same experiment as before on the dismembered details. This time they observed no difference in tail-flipping between the socialized and de-socialized animals. Hence, they concluded that “descending inputs” from the brain likely have something to do with the social history effect on alcohol tolerance.
The findings Swierzbinski and co-workers demonstrate that crayfish subjected to isolation exhibit increased tolerance to alcohol than their social counterparts. While they rightly hesitate to directly translate their findings to humans, the results of the study provide the first hints of a physical change underlying the effects of social history on alcohol consumption—a giant leap toward understanding the effects of social structures on substance abuse.
Abrahim is a PhD student at Scripps Institution of Oceanography in San Diego where he studies marine chemical biology.