title: Systemic apomorphine alters HPA axis responses to interleukin-1 beta administration but not sound stress.
abstract: Apomorphine is a dopamine receptor agonist that was recently licensed for the treatment of erectile dysfunction. However, although sexual activity can be stressful, there has been little investigation into whether treatments for erectile dysfunction affect stress responses. We have examined whether a single dose of apomorphine, sufficient to produce penile erections (50 microg/kg, i.a.), can alter basal or stress-induced plasma ACTH levels, or activity of central pathways thought to control the hypothalamic-pituitary-adrenal axis in rats. An immune challenge (interleukin-1 beta, 1 microg/kg, i.a.) was used as a physical stressor while sound stress (100 dB white noise, 30 min) was used as a psychological stressor. Intravascular administration of apomorphine had no effect on basal ACTH levels but did substantially increase the number of Fos-positive amygdala and nucleus tractus solitarius catecholamine cells. Administration of apomorphine prior to immune challenge augmented the normal ACTH response to this stressor at 90 min and there was a corresponding increase in the number of Fos-positive paraventricular nucleus corticotropin-releasing factor cells, paraventricular nucleus oxytocin cells and nucleus tractus solitarius catecholamine cells. However, apomorphine treatment did not alter ACTH or Fos responses to sound stress. These data suggest that erection-inducing levels of apomorphine interfere with hypothalamic-pituitary-adrenal axis inhibitory feedback mechanisms in response to a physical stressor, but have no effect on the response to a psychological stressor. Consequently, it is likely that apomorphine acts on a hypothalamic-pituitary-adrenal axis control pathway that is unique to physical stressors. A candidate for this site of action is the nucleus tractus solitarius catecholamine cell population and, in particular, A2 noradrenergic neurons.
authors.affiliation: Department of Physiology and Pharmacology, School of Biomedical Science, University of, 4072 Queensland, QLD, Australia. K.Buller@mailbox.uq.edu.au
authors.forename: K M
authors.initials: KM
authors.lastname: Buller
authors.forename: J W
authors.initials: JW
authors.lastname: Crane
authors.forename: S J
authors.initials: SJ
authors.lastname: Spencer
authors.forename: T A
authors.initials: TA
authors.lastname: Day
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology* / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000188:drug therapy; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000008:administration & dosage / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D009622:Noise; D016761:Oncogene Proteins v-fos / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000097:blood; D013315:Stress, Psychological / Q000097:blood
chemical_list: D018491:Dopamine Agonists; D007375:Interleukin-1; D016761:Oncogene Proteins v-fos; D000324:Adrenocorticotropic Hormone; D001058:Apomorphine