Basic Neurobiology of Addiction

Norepinephrine

Norepinephrine (also known as noradrenaline) is widely distributed in the central nervous system. It is involved in arousal, attention, stress, anxiety, and mood disorders. Cell bodies for norepinephrine in the brain originate in the dorsal pons and brainstem (Figure 2.12). The dorsal pons contains the locus coeruleus, which is the source of the dorsal noradrenergic pathway to the cortices and hippocampus. The brainstem projections converge in the ventral noradrenergic bundle to innervate or activate the basal forebrain and hypothalamus. Norepinephrine, particularly in the forebrain, is released in the brain during stressful events and plays an important role in the anxiety/stress-like responses associated with drug dependence. Noradrenergic projections from the locus coeruleus play a key role in maintaining attentional homeostasis (regulating arousal/attention setpoint). For example, both increases and decreases in the activity of norepinephrine in the locus coeruleus are associated with disruptions in working memory.

Norepinephrine binds to three distinct receptors: α1, α2, and β. The α receptor subtypes are coupled to the inositol phosphate second messenger system via Gq proteins, or they inhibit adenylate cyclase by coupling to the inhibitory Gi protein. The β receptor subtype activates adenylate cyclase by coupling to the Gs protein.

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