Abstract:GABAA receptors are the fast inhibitory neurotransmitter receptors, which are important targets for drugs used in the treatment of anxiety disorders, insomnia and anesthesia. while, there are significant risks after the long-time use of these drugs, particularly in tolerance and addiction. Recent findings suggested that those drugs may induce aberrant neuroadaptations in the brain reward circuitry. Recently, benzodiazepines, acting on synaptic GABAA receptors, and modulators of extrasynaptic GABAA receptors (THIP and neurosteroids) have been found to induce plasticity of dopamine neurons in the ventral tegmental area (VTA). Furthermore, populations of synaptic or extrasynaptic GABAA receptor are activated, the repeated administration seems to correlate with rewarding or aversive behavioral responses, respectively. Both synaptic and extrasynaptic GABAA drugs inhibit the VTA GABAergic interneurons, thus activating the VTA DA neurons by disinhibition and this way inducing glutamatergic synaptic plasticity. However, the GABAA drugs failed to alter synaptic spine numbers. Since the GABAergic drugs are known to depress the brain metabolism and gene expression, their likely way of inducing neuroplasticity in mature neurons is by disinhibiting the principal neurons, which remains to be tested.

Key words:GABAA receptor,benzodiazepines,dendritic spines,dopamine neurons,neuroadaptation,neurosteroids