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Keywords:

  • amphetamine;
  • HPA-axis;
  • interleukin-1;
  • rat;
  • stress-sensitization

Abstract

Single administration of the cytokine interleukin-1α (IL-1), or the psychostimulant amphetamine, enhanced adrenocorticotropin hormone and corticosterone responses to a stress challenge weeks later. This long-lasting hypothalamic-pituitary-adrenal (HPA)-sensitization is paralleled by an increase in electrically evoked release of noradrenaline in the paraventricular hypothalamic nucleus (PVN). We hypothesized that these functional changes may be associated with morphological plasticity of noradrenergic projections to the PVN, a parameter that shows high reproducibility. Specific alterations in relative (nor)adrenergic innervation density were studied by using dopamine-α-hydroxylase (DBH) as a marker. An image analysis system was used to detect changes in the relative DBH innervation density of the PVN. Groups of adult male rats were given IL-1 (10 µg/kg i.p.), amphetamine (5 mg/kg i.p.), or saline. Three weeks later, IL-1 and amphetamine primed rats showed enhanced adrenocorticotropin hormone and corticosterone responses to an amphetamine challenge. In another set of experiments, the relative DBH innervation density was measured in different PVN subnuclei at four rostro-caudal levels. Single administration of either IL-1 or amphetamine causes three weeks later a selective decrease in relative DBH innervation density in those subnuclei of the PVN that contain high numbers of corticotrophin-releasing hormone (CRH) producing neurons: the dorsal parvocellular and medial parvocellular PVN. We conclude that (1) long-lasting sensitization induced by single exposure to IL-1 and amphetamine induces specific pattern of neuroplastic changes in (nor)adrenergic innervation in the PVN and (2) reduction of relative DBH innervation density in CRH-rich areas is associated with paradoxical increase of electrically evoked release of (nor)adrenaline.