Chapter 9 Pregnane Steroids and Short-Term Neural Plasticity

Gamma-aminobutyric acid (GABA) is the major inhibitory transmitter in the brain, and its fast effects are mediated by the GABA-A receptor. It is well known, from pharmacological manipulations, that many exogenous agents alter the efficacy of GABA-A receptors. For example, benzodiazepines increase the effect of GABA and some β-carbolines reduce the effect of GABA at these receptors. Increasing the strength of neuronal inhibition can prevent seizures, reduce anxiety and be neuroprotective. There are also endogenous mechanisms that increase effi- cacy. For example, more GABA-A receptors can be synthesized and inserted into synapses, but this requires up to 1 h or more. On a shorter timescale, GABAergic inhibition can be potentiated by steroids, e.g., allopregnanolone, synthesized de novo in neural tissue or derived from peripheral endocrine organs. The widespread distribution of these neuroactive steroids across the brain suggests an extensive role in short-term neural plasticity.