We have all heard about the problems that can occur when people are exposed to drugs of various kinds as adolescents. The media abounds with stories of “pharming parties”, drinking teens, and stories of lives gone wrong. Adolescence is a very tricky period of life. Teens are thought to be at more risk to suffer the negative consequences of drug use, as the adolescent brain is a changing brain, one undergoing extensive neuronal and connective remodeling. We usually think of this in terms of whole cells growing and dying, connections forming or going away. And this does happen, but there are also more subtle effects, like changes in the receptors that mediate signaling in the brain.
One major example of this is the GABA receptor. GABA stands for gamma-Aminobutyric acid, and this chemical is the most important inhibitory neurotransmitter in the brain. Increases in GABA release generally result in decreased cellular activity on the cells where GABA acts directly. But remember (as Sci will tell you often), a chemical is ONLY as good as its receptor! GABA has receptors that are comprised of several different subunits which form up together, and the subunit composition of the receptors determines how a cell will respond to GABA signaling.
And the composition of these GABA receptors is one of the things that changes during adolescence. But what if you take drugs that affect GABA during this time of receptor change? Will this change how you react to drugs such as alcohol (which exerts some of its effects via GABA) during adulthood?
Worrel, Amato, Winsauer. “GABA-A receptor modulation during adolescence alters adult ethanol intake and preference in rats” Louisiana State University Health Sciences Center, presented at Experimental Biology, 2011.
To produce changes in GABA receptor modulation during adolescence, Worrel et al took groups of adolescent rats and gave them either a positive modulator of the GABAA receptor (lorazepam, an antianxiety drug that is marketed as Ativan), or a negative modulator of the GABAA receptor (Dehydroepiandrosterone or DHEA, a neurosteroid which, among other things, acts as a modulator of GABA with negative effects, and which you can buy over the counter at health food stores). They administered the drugs to the rats every other day during adolescence, and looked at how they developed and how they responded to alcohol in adulthood.
They found that, during adolescence, the lorazepam increased food intake on the days when it was given, while DHEA had the opposite effect. They then waited until the rats were adults, and looked at their alcohol drinking.
When they gave the now adult rats exposure to different concentrations of alcohol (5, 10, or 18{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} ethanol with some saccharin in there), they found that all animals decreased intake of alcohol as the dose increased, titrating the dose as they go. They found differences in the alcohol intake during adulthood, depending on whether the rats were treated with lorazepam or DHEA in adolescence (those treated with lorazepam drank more of low concentration ethanol), AND they found a significant change in adulthood of how the rats consumed alcohol vs another, nonalcoholic sweet drink.ignificant change in adulthood of how the rats consumed alcohol vs another, nonalcoholic sweet drink. In rats treated with lorazepam in adolescence, as their alcohol consumption decreased (when the dose got higher) their choice for the non-alcoholic sweet drink increased (as you might expect, rats love a good sweet drink). But the rats treated with DHEA did not show preference for the non-alcoholic sweet drink, even when their intake of the alcoholic drink decreased.
This is clearly a preliminary study, DHEA is not particularly selective, and the authors plan to conduct more studies to try and understand why the animals treated with lorazepam show differences in their preference for sweetened solutions. But it does show that dosing with drugs that affect GABA-A receptors during adolescence can significantly change how animals react to alcohol in adulthood, by changing their preferences for alcoholic vs non-alcoholic solutions. And both of the drugs used, lorazepam and DHEA, are drugs that are in use currently in America. Lorazepam is prescribed as an antianxiety drug, while DHEA is sometimes used in body building, and is also in studies for potential treatment of depression. This means that adolescents can gain access to these drugs, and other drugs like them, increasing the likelihood that they will be exposed to GABA modulation via drugs like these in adolescence. This makes it important to understand exactly how changes in GABA receptors can affect animals and humans in adolescence and beyond, as we all get exposed to the drugs around us.
