Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective GABA_A Receptor Modulators?

Table 1

Localization of common GABA_A receptor subtypes in the brain (adapted from [19]).

Subtype	Frequency	Localization
α 1β 2γ 2	Major (60%) synaptic	Cerebral cortex (layer I–VI), hippocampus, striatum, cerebellum, amygdala, brainstem.
α 2β nγ 2	Minor (15–20%) synaptic	Cerebral cortex (layers I–IV), hippocampus, striatum, hypothalamus, amygdala.
α 3β nγ 2	Minor (10–15%) synaptic	Cerebral cortex (layers V-VI), hippocampus, cerebellum, amygdala, brainstem (including raphe nuclei and locus coeruleus), spinal cord.
α 4β nδ/γ	Minor (<10%) extrasynaptic	Hippocampus (dentate gyrus), thalamus, cortex.
α 5β nγ 2	Minor (<5%) extrasynaptic	Cerebral cortex, hippocampus, amygdala, hypothalamus, spinal cord.
α 6β nγ2/δ	Minor (<5%)(extra) synaptic	Cerebellum.