Introduction
Adolescence: What, why    and when?
Adolescent brain    development
Adolescent substance use
Alcohol affects adolescents    differently
Long-term effects
Summary
References
   

Alcohol affects adolescents and adults differently in many ways
     It has become quite clear over recent years that alcohol impacts both behavior and brain function differently in adolescents and adults. This general finding should perhaps not be surprising given the dramatic changes in brain occurring during the adolescent period. Recent studies suggest that adolescents are more vulnerable to some effects of alcohol exposure, while being less vulnerable to others. These findings will be reviewed below, beginning with the impact of alcohol on memory and memory-related brain function in general, and then focusing on developmental differences in these effects. Differences in the impact of alcohol on sedation and motor coordination in adolescents and adults will then be discussed.

Learning and memory
     It is well known that alcohol produces learning and memory impairments. These effects are reviewed in detail on a separate page (click here). Briefly, alcohol primarily interferes with the establishment of new memories rather than the recollection of previously stored information. Alcohol produces what Ryback (1971) referred to as a continuum of encoding deficits. That is, as the dose of alcohol goes up, the magnitude of the memory impairments go up, as well. For instance, while a few drinks might make it more difficult for you to learn a new person's name, a bunch of drinks might completely impair your ability to remember ever having met the person at all. The inability to remember entire events that occurred while drinking is commonly referred to as a blackout (click here for more about blackouts).
     The specific mechanisms by which alcohol impairs memory are still under investigation. However, it seems likely that alcohol does so by disrupting neural plasticity in brain regions involved in memory formation. Neural plasticity refers to the ability of circuitry in the brain to reorganize itself as a result of experience. The altered activity in neural circuits somehow represents the acquired information and allows for the recollection of the information at a later time. Alcohol appears to interfere with the changes in circuitry that occur during learning.
     One brain region that is highly involved in memory formation and exhibits a tremendous amount of neural plasticity is the hippocampus. The hippocampus is an old cortical structure located deep within a region of the brain known as the temporal lobes (see the figure below). The temporal lobes run along the sides of your brain at about the level of the temples. For a detailed discussion of the role of the hippocampus in learning and memory, please click here.

Location of the hippocampus

Location of the hippocampus in the human brain
(This image was borrowed from www.morphonix.com, a site offering multimedia software aimed at educating children and adults about the brain)

     Alcohol disrupts the functioning of the hippocampus. This has been demonstrated using a variety of methods, including the recording of hippocampal neurons in freely behaving animals (White and Best, 2000). The effects of alcohol on hippocampal function have also been assessed in a variety of experiments examining the impact of alcohol on Long-Term Potentiation (LTP). LTP is a model of the changes in hippocampal circuitry that might occur during learning. LTP is not learning. It is simply a model for what might occur in the brain during learning. Nonetheless, LTP offers an interesting way of assessing the impact of drugs like alcohol on neural plasticity, and for comparing the effects of alcohol on memory-related brain function in adolescent and adults subjects. LTP experiments are typically carried out using slices of tissue removed the brain and kept alive by bathing them in oxygenated artificial cerebral spinal fluid (ACSF), which is essentially the same stuff that keeps our brains alive inside of our bodies. The figure below shows the location of the the hippocampus in the rat brain and a diagram of a slice of hippocampal tissue.

Location of the hippocampus in rats

Location of the hippocampus in the rat brain
[From: Fuster, J.M. Memory in the Cerebral Cortex: An Empirical Approach to Neural Networks in the Human and Nonhuman Primate. Cambridge, Massachusetts: The MIT Press, 1995, p26.]
     In a typical LTP experiment, two electrodes are lowered into the slice of tissue. The positioning of these electrodes is indicated by the letters A and B in the figure below. A small amount of current is passed through electrode A, causing the neurons in this area to send signals to cells located near electrode B. Electrode B then records the response of cells in the area to the incoming signals. This response is referred to as the baseline response. Next, a specific pattern of stimulation intended to model the pattern of activity that might occur during an actual learning event is delivered through electrode A. Now, when you return to the original stimulus delivered during baseline, the response recorded at B is bigger (i.e., potentiated). In other words, as a result of the patterned input, cells at position B are now more responsive to signals sent from cells at position A. The potentiated response often lasts for a long time, hence the label Long-Term Potentiation.        

Slice of hippocampus from rat

     Alcohol interferes with the establishment of LTP. If there is enough alcohol in the brain when you give the patterned stimulus, the response recorded later at position B will not be bigger than it was during baseline. Because drugs that interfere with the establishment of LTP also cause memory impairments in humans, many people believe that LTP serves as a good model for studying the neurobiology underlying the effects of drugs like alcohol on memory. Two recent studies have revealed that adolescent brains are much more sensitive to the effects of alcohol on LTP than adults (Swartzwelder et al., 1995; Pyapali et al., 1999).
     One of the key requirements for the establishment of LTP in the hippocampus is that a particular type of neurotransmitter recepter, called the NMDA receptor, becomes activated. Activation of the NMDA receptor allows calcium (CA++) to enter the cell, which sets off a chain of events leading to long-lasting changes in the structure and/or function of the cell. Alcohol interferes with the activation of the NMDA receptor, thereby preventing the influx of CA++ and the changes that follow. This is believed to be the mechanism underlying the effects of alcohol on LTP induction. (Click here for a diagram of an NMDA receptor and more on the effects of alcohol on NMDA receptor functioning). It is now clear that alcohol has a much bigger impact on NMDA receptor activation in adolescents than in adults (Swartzwelder et al., 1995). Differences in the affects of alcohol on NMDA receptor activity in the hippocampus of adolescents and adults provides a logical explanation for differences in the affects of alcohol on LTP in these age groups. Further, these differences suggest that we might expect adolescents to be more vulnerable than adults to the affects of alcohol on learning and memory.
     The available evidence suggests that adolescents are more vulnerable than adults to the affects of alcohol on learning and memory, though much more work needs to be done in this area. In rats, one task commonly used to assess learning and memory is called the Morris water maze task. This task requires rats to located a platform submerged an inch or so beneath the surface of the water in a big circular tub (see below). The ability to learn this task is very sensitive to changes in activity in the hippocampus, so it provides an easy way to assess whether drugs that disrupt hippocampal function also disrupt learning that is dependent on this structure. Markwiese et al. (1998) discovered that adolescent rats are much more vulnerable to alcohol-induced learning impairments in the water maze than adults.       

The Morris water maze task      

The Morris water maze task
The rat is required to learn the location of a platform submerged an inch or so beneath the surface of the water. Alcohol impairs performance in this task, and does so more potently in adolescents than adults.
     It is difficult to determine whether adolescent humans, like adolescent rats, are more vulnerable than adults to the effects of alcohol on learning and memory. For obvious legal and ethical reasons, this research has not been carried out in young adolescent humans. However, the neurobiology underlying memory formation is considered to be, at a basic level, similar between rats and humans, leading us to expect similar outcomes at the behavioral level. In fact, recent evidence suggests that people in their early twenties are actually more vulnerable to alcohol-induced memory impairments than those in their late twenties (Acheson et al., 1999). While people in their early twenties are arguably outside of the adolescent age range, the data certainly suggest that younger subjects are more vulnerable to alcohol-induced memory impairments than slightly older subjects, raising the possibility that true adolescents are even more vulnerable still.
     In the aforementioned study, subjects were tested using a variety of tasks, including the complex figure task. In this task, subjects were shown a line drawing and were required to reproduce the drawing immediately after it was shown to them (immediate recall ) and then again twenty minutes later (delayed recall). The figure below shows an example of a complex figure, and the effects of alcohol on performance of subjects in the two age groups. When tested under placebo, all subjects performed similarly in both the immediate and delayed components of the task. However, when tested under alcohol (the equivalent of about 2-3 drinks), subjects in their early twenties performed worse than subjects in their late twenties on both components of the task.      
Alcohol produces bigger working memory impairments in younger drinkers

Alcohol and the complex figure task
Subjects were shown a figure like the one in the upper left and were asked to recreate it both immediately after seeing it and twenty minutes later. Alcohol impaired performance more in subjects between 21-24 years of age than in subjects 25-29 years of age.

Sleepiness (sedation) and problems with balance and muscle coordination
      While younger subjects appear to be more sensitive than adults to the affects of alcohol on learning and memory, recent evidence suggests that they might actually be less sensitive to other effects. For instance, a number of reports suggest that adolescent rats are less vulnerable than adults to alcohol-induced sedation. Sedation refers to the calming or tranquilizing effects a drug. In rats, sedation is often assessed by examining something called the righting reflex. If you lay a rat on its back, it quickly turns over (i.e., rights itself). Drugs with sedative effects, like alcohol, suppress the righting reflex. For instance, after being given a big dose of alcohol, rats will let you lay them on their backs without attempting to right themselves. The extent of sedation is commonly assessed by simply testing how long it takes after drug treatment for a rat to regain its righting reflex. It has been demonstrated numerous times over the past few years that adolescent rats are significantly less sensitive than adults to the effects of alcohol on the righting reflex (Little et al., 1996; Swartzwelder et al., 1998; Silveri and Spear, 1998). These findings suggest that the sedative effects of alcohol are weaker in adolescents than adults.
     It also appears that adolescents might be less sensitive than adults to the effects of alcohol on motor coordination. Motor coordination refers to the ability to maintain balance, to walk without stumbling, to drive a car with a manual transmission, etc. As is well known, alcohol disrupts motor coordination. Indeed, the impact of alcohol on motor coordination serves as the basis for field sobriety tests. A limited amount of research, again with rats, suggests that alcohol affects motor coordination to a lesser degree in adolescents than adults (Hollstedt and Rydberg, 1985; White et al., 2001; White et al., submitted). The effects of alcohol on motor coordination are commonly assessed using a simple device called a tilting plane (see Figure below). As the name implies, the rat is placed on a flat, typically glass, surface and one end of the surface is slowly raised. Staying on the surface without sliding requires coordinated motor activity. The angle at which the subject slides is assessed while sober and intoxicated, and the data are then compared. It is quite clear that adolescent rats are much less affected by alcohol in this task than adults, suggesting that they might be less vulnerable to alcohol-induced motor impairments.

The tilting plane task is used to assess the effects of alcohol on balance and muscle coordination in rats

Alcohol impairs balance and muscle coordination
The tilting plane apparatus and depictions of performance of a subject while sober (a) and intoxicated (b). Alcohol reduces the angle at which subjects begin to slide
     The figure below shows the effects of alcohol on performance of the tilting plane test in adolescent and adult rats (White et al., 2001). It is quite clear that adolescent rats are much less affected by alcohol in this task than adults, suggesting that they might be less vulnerable to alcohol-induced motor impairments.
Alcohol impairs balance more in adult rats than in adolescent rats
Alcohol impairs balance and muscle coordination more in adult rats than in adolescent rats
The graph shows the effects of 1.5 g/kg alcohol on balance and muscle coordination in adolescent and adult rats (n=6 per group). Adolescent subjects were less impaired than adults at both 10 and 30 min post-injection. (* = between group difference, a = difference relative to baseline for adolescent subjects, b = difference relative to baseline for adult subjects. All p-values less than 0.05)
     The existing research regarding alcohol-induced sedation and motor impairments in adolescents and adults has all involved the use of rats. In humans, the sedative and motor incoordinating effects of alcohol can limit the amount of alcohol an individual consumes. That is, the individual might find him/herself incapacitated at some point during the evening and unable to continue drinking even if they desired to do so. If the findings observed with rodents extend to humans, the decreased vulnerability of adolescents to the sedative and motor impairing effects of alcohol might allow adolescents to continue drinking for longer periods of time than adults, and perhaps achieve much higher BACs, without becoming incapacitated. As we have seen, adolescents appear to be more vulnerable than adults to some of the cognitive impairments produced by alcohol. Thus, the reduced susceptibility to alcohol-induced sedation and motor incoordination, combined with an enhanced susceptibility to alcohol-induced cognitive deficits, could be a potentially very dangerous combination of effects. Clearly, the above model depends upon the assumption that adolescent humans are, in fact, less vulnerable than adults to the sedative and motor incoordinating effects of alcohol. This has not yet been demonstrated scientifically, though we expect it to be the case.
     In addition to greater short-term risks associated with alcohol use during adolescence, recent research strongly suggests that adolescents might also be at greater risk for long-term deficits following alcohol abuse. These findings will be covered in the next section.        
 
   
   
   
   
Hit counter
   
Adolescent substance use
Long-term effects