Acid (GABA) Receptors in the Mammalian Central

-Aminobutyric acid (GABA), the major inhibitory neuro-transmitter in the mammalian central nervous system, is a neutral amino acid synthesized presynaptically from glutamic acid by the rate-limiting enzyme glutamic acid decarboxy-lase.1 GABA, released from presynaptic neurons, binds to at least two classes of receptors (ie, GABAA and GABAB), which are found on almost all cortical neurons.2 The exis-tence of GABAC receptors (which are found predominantly in the retina) has been known for years but, owing to their structural and pharmacologic similarity to GABAA receptors, have not been categorized separately in most classification schemes. GABAA receptors are also found on neuroglia, although the functional significance of this localization is not entirely clear.3 Although much is known about the distribution of GABAergic synapses and neurons in various regions of the brain, less is understood regarding the ontogeny of these GABAergic systems and the age-specific roles of GABA in synaptic integration. As early as embryonic day 15 (E15), glu-tamic acid decarboxylase messenger ribonucleic acid (RNA) and protein can be detected in whole rat brain.4–6 Glutamic acid decarboxylase messenger RNA and protein levels increase rapidly in late fetal life and persist through adult-hood; however, the proportion of glutamic acid decar-boxylase messenger RNA relative to total RNA remains relatively constant in postnatal rat. Basal GABA synthesis rates in immature rat pups have been measured with high-performance liquid chromatography and increase progres-sively over the first postnatal month, both in the neocortex and the hippocampus.7 GABAA RECEPTORS The GABAA receptor is a macromolecular receptor complex containing binding sites for agonists and a number of allosteric modulators (such as benzodiazepines and barbi-turates), each differentially affecting the kinetic properties of the receptor.8,9 This receptor is a heteropentameric com-plex composed of combinations of several polypeptide sub-units arranged in topographic fashion to form an ion channel