Drug Discovery Opinion

Puberty is a time of great physical and emotional changes and studies have shown that some skills are most easily acquired before – or after – puberty. Working with mice, scientists at SUNY Downstate Medical Center in Brooklyn have now been able to suggest a reason for the observed reduction in learning ability seen in adolescents. They have shown that there is a temporary increase in levels of the α4βδ GABA-A receptor in the hippocampus during puberty. The hippocampus plays key roles in spatial learning and memory and increases in levels of the receptor reduce brain excitability and impair spatial learning. Levels of α4βδ GABA-A receptor were found to increase at puberty, falling back to an intermediate level when the animals reached maturity. Pubescent mice were found to be much less able to master a test of spatial learning than prepubescent animals. The team also showed that the learning disability could be reversed by administration of the stress steroid, THP. In human children and adults, THP reduces brain activity and has a tranquilizing effect; in pubescent mice, the hormone increases activity in the hippocampus and has the opposite effect.

The study suggests that intrinsic learning mechanisms alter during adolescence and that the temporary decline in learning ability might be reversed in middle school by different teaching and motivation strategies which involve mild stress. If findings from the mouse studies are applicable to human teenagers, compounds targeting the α4βδ GABA-A receptor may also prove useful, especially for adolescents with learning difficulties.

The study is published in the journal Science.

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