Cytokines, Stress, and Depression

Volume 461 of the series Advances in Experimental Medicine and Biology pp 117-127

Effects of Cytokines on Cerebral Neurotransmission

Comparison with the Effects of Stress
  • Adrian J. DunnAffiliated withDepartment of Pharmacology and Therapeutics, Louisiana State University Medical Center
  • , Jianping WangAffiliated withInflammatory Joint Diseases Section, NIAMS/NIH
  • , Tetsuya AndoAffiliated withNational Institute of Mental Health, National Center of Neurology and Psychiatry, Division of Psychosomatic Research

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Stress is normally associated with coactivation of the sympathoadrenal system (sympathetic nervous system plus the adrenal medulla) and the hypothalamo-pituitary-adrenocortical (HPA) axis. However, extensive work in the past 30 years has indicated that responses also occur in the central nervous system. The major response occurs in noradrenergic (NA) neurons. Most studies have also noted responses in dopaminergic (DA) and serotonergic (5-HT) systems (Dunn & Kramarcy, 1984; Stone, 1975). Whether or not adrenergic (adrenaline-containing) neurons respond is not resolved, although there is evidence that adrenergic neurons (along with NA and 5-HT neurons) are involved in the regulation of hypothalamic corticotropin-releasing factor (CRF) secretion which initiates HPA activation (Plotsky, Cunningham, & Widmaier, 1989). The NA response is widespread and appears to affect to similar extents both the locus coeruleus (A6) system innervating the dorsal structures (cortex, hippocampus, cerebellum, etc.), and the nucleus tractus solitarius (A1/A2) system innervating the ventral structures (e.g., the hypothalamus). The DA response is also widespread with all the major neuronal systems (nigrostriatal, mesolimbic, mesocortical) showing responses, but the magnitude of the response is particularly large in the mesocortical system (i.e. in the prefrontal and cingulate cortices). The 5-HT response is not markedly regionally specific (although some (e.g., Kirby, Allen, & Lucki, 1995) have reported regional differences). There is also a robust elevation of concentrations of tryptophan (the natural precursor of 5-HT) in all regions of the brain.