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α 1 -adrenergic receptors are G-Protein Coupled Receptors that are involved in neurotransmission and regulate the sympathetic nervous system through binding and activating the neurotransmitter, norepinephrine, and the neurohormone, epinephrine. There are three α 1 -adrenergic receptor subtypes (α 1A , α 1B , α 1D ) that are known to play various roles in neurotransmission and cognition. They are related to two other adrenergic receptor families that also bind norepinephrine and epinephrine, the β- and α 2 -, each with three subtypes (β 1 , β 2 , β 3 , α 2A , α 2B , α 2C ). Previous studies assessing the roles of α 1 -adrenergic receptors in neurotransmission and cognition have been inconsistent. This was due to the use of poorly-selective ligands and many of these studies were published before the characterization of the cloned receptor subtypes and the subsequent development of animal models. With the availability of more-selective ligands and the development of animal models, a clearer picture of their role in cognition and neurotransmission can be assessed. In this review, we highlight the significant role that the α 1 -adrenergic receptor plays in regulating synaptic efficacy, both short and long-term synaptic plasticity, and its regulation of different types of memory. We will also present evidence that the α 1 -adrenergic receptors, and particularly the α 1A -adrenergic receptor subtype, are a potentially good target to treat a wide variety of neurological conditions with diminished cognition.

α1-Adrenergic Receptors in Neurotransmission, Synaptic Plasticity, and Cognition