Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- Acknowledgements and Disclosures -- Introduction: revision of an old transmitter -- Part I The neurobiology of norepinephrine -- 1 Neuroanatomical and chemical organization of the locus coeruleus -- Early history of the locus coeruleus -- Species comparisons -- Ontogeny -- Morphological and ultrastructural characteristics -- Transmitter identity and receptor distribution -- Connections: sources of afferent input to LC -- The LC efferent projection -- Chemoarchitecture: neurochemically identified pathways -- Overview -- REFERENCES -- 2 Interactions of norepinephrine with other neurotransmitter systems: anatomical basis and pharmacology -- Introduction -- Noradrenergic circuitry: input to the LC -- Noradrenergic circuitry: reciprocal output from the LC -- Summary and conclusions -- Acknowledgements -- REFERENCES -- 3 Receptors for norepinephrine and signal transduction pathways -- Introduction -- Adrenergic receptor subtypes -- Characteristics of alpha1-adrenergic receptors -- Characteristics of alpha2-adrenergic receptors -- Characteristics of beta-adrenergic receptors -- Signal transduction pathways -- Physiological roles -- Conclusions/summary -- REFERENCES -- 4 Regulation of gene transcription in the central nervous system by norepinephrine -- Introduction -- Fundamental concepts of gene transcription -- Noradrenergic receptors couple to multiple signal transduction cascades and transcription factors -- Role of noradrenergic receptor regulation of transcription factors and gene expression in the actions of antidepressant treatment -- Antidepressants and norepinephrine regulation of c-fos gene expression and AP-1 DNA binding -- Role of NE-CREB signaling in learning and memory -- Conclusions -- Acknowledgements -- REFERENCES -- 5 The norepinephrine transporter and regulation of synaptic transmission -- Introduction -- The norepinephrine transporter and the importance of norepinephrine uptake -- Regulation of norepinephrine uptake -- Norepinephrine transporter-associated proteins -- Norepinephrine transporter gene, polymorphisms and splice variants -- Clearance of norepinephrine and aging -- Norepinephrine transport and disease -- Conclusions -- Acknowledgements -- References -- Part II Norepinephrine and behavior -- 6 Role of the locus coeruleus-norepinephrine system in arousal and circadian regulation of the sleep-wake cycle -- Introduction -- Brain systems involved in sleep-wake regulation -- LC involvement in sleep-wake regulation -- Role of corticotropin-releasing factor in noradrenergic regulation of sleep and waking -- Role of LC in circadian regulation of sleep and waking -- Clinical perspectives: LC participation in sleep alterations due to clinical pathologies -- Conclusions -- REFERENCES -- 7 The locus coeruleus and regulation of behavioral flexibility and attention: clinical implications -- Introduction -- Background -- Recent results recording LC neurons in behaving monkeys -- Computational modeling: simulation of LC activity and task performance -- Decision-related activation of monkey LC neurons -- Influence of prefrontal cortex on activity of LC neurons -- Discussion -- Clinical implications -- Hypertonic LC activity: attention-deficit/hyperactivity disorder and posttraumatic stre