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NeuropharmacologyCellular, synaptic and molecular mechanisms of action of central nervous system drugs; especially barbiturates, opiates, anesthetics, abused inhalants and new experimental drugs. We use electrophysiological recording techniques and selective pharmacological probes, in hippocampal and cortical brain slices, to investigate sites and mechanisms of action for CNS active agents. The long-term goal of our studies is to provide physiological background information required for the rational design of safer and more effective drugs for anesthesia. Our recent studies have focussed on anesthetic effects at glutamate and GABA-mediated synapses as important targets for the CNS depressant effects of these agents. Depressed glutamate-mediated excitatory neurotransmission appears to be a common effect produced by most general anesthetics. We are currently studying agent specific actions at AMPA and NMDA glutamate receptor subtypes. Enhanced GABA-mediated inhibitory neurotransmission also appears to play an important role for many anesthetics. Anesthetics act at both pre- and post-synaptic sites to alter neurotransmission in higher brain centers. Thus, discrete synaptic targets could provide fruitful avenues for the development of safer and more effective therapeutic agents for analgesia and anesthesia.