Biochemical and anatomical substrates of depression and sickness behavior.
This paper reviews recent research on the contribution of the proinflammatory cytokine interleukin-1 (IL- 1) and the purine nucleoside adenosine in mediating behavioral depression and related symptoms of conservation-withdrawal in animal models of both major depression and illness. Activation of brain IL- 1 receptors appears to contribute to conservation withdrawal symptoms in animals treated with reserpine or lipopolysaccharide, suggesting a common underlying mechanism. Moreover, brain cytokine signaling is capable of recruiting adenosine signaling at adenosine A2A receptors, which directly mediate symptoms of behavioral depression. The adenosine receptors densely populate spiny GABAergic neurons in the striopallidal tract in the striatum and form part of an A2A/D2/mGLU receptor complex. Activation of these A2A receptors functionally uncouples dopamines excitatory motivation influence from ongoing behavior, leading to a state of conservation-withdrawal, and antagonism of the ventral medial striatum A2A receptors in reserpinated rats relieves symptoms of behavioral depression.
Hanff
Thomas C
TC
Department of Psychology, University of California, Los Angeles, California 90095-1563, USA.
Furst
Stephanie J
SJ
Minor
Thomas R
TR
D000241:Adenosine / Q000378:metabolism*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003863:Depression / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D055809:Illness Behavior; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D005680:gamma-Aminobutyric Acid; D012110:Reserpine; D000241:Adenosine; D004298:Dopamine