Fundamental to the activity of the brain is the controlled balance between excitation and inhibition, with the substance GABA being the major inhibitory neurotransmitter present in the mammalian brain. As such, there is considerable interest in furthering our understanding of the role and regulation of GABA. The research carried out by this group is directed towards the development of drugs that selectively act on different types of GABA receptors, transporters and related membrane proteins. This work involves structure-activity studies, carried out on specific receptors expressed in oocytes and other test systems, as well as computer-assisted modelling to identify novel compounds to be investigated as neuroactive substances. Such substances may prove useful in the treatment of a number of disorders in which the brain's balance of excitation and inhibition is disturbed, notably including: Alzheimer's disease, anxiety, diabetes, epilepsy and schizophrenia.
One particular arm of our research is looking at the role of ionotropic GABA receptors in schizophrenia. GABA-A receptors have a pivotal role in the brain, as they are crucial for brain development, are modulated by substances released during stressful events, and are altered in schizophrenia. We are investigating the "two-hit" stress hypothesis to examine whether neonatal stress, coupled with adolescent stress, confers vulnerability to schizophrenia by altering GABA-A receptor expression and behaviours subserved by these receptors. Other research projects include examining the effects of antipsychotic medications on GABA-A receptor expression using animal administration models and receptor function using electrophysiological recording from recombinant receptors expressed in Xenopus oocytes. We are also using field research methods on a clinical population of schizophrenia sufferers to examine quality of life and the effects of antipsychotic medications.