The biological impact of living with chronic breathlessness – A role for the hypothalamic–pituitary–adrenal axis?

Ryan, R., Spathis, A., Clow, A., Fallon, M. and Booth, S. 2014. The biological impact of living with chronic breathlessness – A role for the hypothalamic–pituitary–adrenal axis? Medical Hypotheses. 83 (2), pp. 232-237. https://doi.org/10.1016/j.mehy.2014.04.011

TitleThe biological impact of living with chronic breathlessness – A role for the hypothalamic–pituitary–adrenal axis?
AuthorsRyan, R., Spathis, A., Clow, A., Fallon, M. and Booth, S.
Abstract

Breathlessness is a common and distressing symptom in advanced cardiorespiratory disease, with recognised
psychological, functional and social consequences. The biological impact of living with chronic
breathlessness has not been explored. As breathlessness is often perceived as a threat to survival, we propose
that episodic breathlessness engages the stress-response, as regulated by the hypothalamic–pituitary–
adrenal (HPA) axis. Furthermore, we hypothesise that chronic breathlessness causes excessive
stimulation of the HPA axis, resulting in dysfunctional regulation of the HPA axis and associated neuropsychological,
metabolic and immunological sequelae. A number of observations provide indirect support
for this hypothesis. Firstly, breathlessness and the HPA axis are both associated with anxiety. Secondly,
similar cortico-limbic system structures govern both breathlessness perception and HPA axis regulation.
Thirdly, breathlessness and HPA axis dysfunction are both independent predictors of survival. There is a
need for direct observational evidence as well as experimental data to investigate this hypothesis which,
if plausible, could lead to the identification of a new biomarker pathway to support breathlessness
research.

JournalMedical Hypotheses
Journal citation83 (2), pp. 232-237
ISSN0306-9877
Year2014
PublisherElsevier
Digital Object Identifier (DOI)https://doi.org/10.1016/j.mehy.2014.04.011
Publication dates
Published13 Apr 2014
PublishedAug 2014
FunderNIHR (National Institute for Health Research)

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Hucklebridge, F., Mellins, J., Evans, P. and Clow, A. 2002. The awakening cortisol response: no evidence for an influence of body posture. Life Sciences. 71 (6), pp. 639-646. https://doi.org/10.1016/S0024-3205(02)01726-5

Neuroimmune relationships in perspective
Clow, A. and Hucklebridge, F. 2002. Neuroimmune relationships in perspective. International Review of Neurobiology. 52 (1), pp. 1-15.

Ultrasound measures of bone and the diurnal free cortisol cycle: a positive association with the awakening cortisol response in healthy premenopausal women
Brooke-Wavell, K., Clow, A., Ghazi-Noori, S., Evans, P. and Hucklebridge, F. 2002. Ultrasound measures of bone and the diurnal free cortisol cycle: a positive association with the awakening cortisol response in healthy premenopausal women. Calcified Tissue International. 70 (6), pp. 463-468. https://doi.org/10.1007/s00223-001-2085-8

Low frequency noise enhances cortisol among noise sensitive subjects during work performance
Persson Waye, K., Bengtsson, J., Rylander, R., Hucklebridge, F., Evans, P. and Clow, A. 2002. Low frequency noise enhances cortisol among noise sensitive subjects during work performance. Life Sciences. 70 (7), pp. 745-758. https://doi.org/10.1016/S0024-3205(01)01450-3

Association between time of awakening and diurnal cortisol secretory activity
Edwards, S., Evans, P., Hucklebridge, F. and Clow, A. 2001. Association between time of awakening and diurnal cortisol secretory activity. Psychoneuroendocrinology. 26 (6), pp. 613-622. https://doi.org/10.1016/S0306-4530(01)00015-4

Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity
Edwards, S., Clow, A., Evans, P. and Hucklebridge, F. 2001. Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity. Life Sciences. 68 (18), pp. 2093-2103. https://doi.org/10.1016/S0024-3205(01)00996-1

CuZn-superoxide dismutase transgenic mice: no effect on longevity, locomotor activity and 3H-mazindol and 3H-spiperone binding over 19 months
Gallagher, I., Jenner, P., Glover, V. and Clow, A. 2000. CuZn-superoxide dismutase transgenic mice: no effect on longevity, locomotor activity and 3H-mazindol and 3H-spiperone binding over 19 months. Neuroscience Letters. 289 (3), pp. 221-223. https://doi.org/10.1016/S0304-3940(00)01279-9

Modulation of secretory immunoglobulin A in saliva; response to manipulation of mood
Hucklebridge, F., Lambert, S., Clow, A., Warburton, D.M., Evans, P. and Sherwood, N. 2000. Modulation of secretory immunoglobulin A in saliva; response to manipulation of mood. Biological Psychology. 53 (1), pp. 25-35. https://doi.org/10.1016/S0301-0511(00)00040-5

The cortisol response to normal and nocturnal awakening
Hucklebridge, F., Clow, A., Rahman, H. and Evans, P. 2000. The cortisol response to normal and nocturnal awakening. Journal of Psychophysiology. 14 (1), pp. 24-28. https://doi.org/10.1027//0269-8803.14.1.24

Mind, immunity and health: the science of psychoneuroimmunology
Evans, P., Hucklebridge, F. and Clow, A. 2000. Mind, immunity and health: the science of psychoneuroimmunology. London Free Association.

Endogenous monoamine oxidase inhibitory activity and HPA activation in the pig
Clow, A., Vellucci, S.V., Parrott, R.F., Hucklebridge, F., Sen, S. and Evans, P. 1999. Endogenous monoamine oxidase inhibitory activity and HPA activation in the pig. Life Sciences. 66 (1), pp. 35-41. https://doi.org/10.1016/S0024-3205(99)00559-7

Long term effects of pergolide and (-)-deprenyl on 3H-mazindol and 3H-spiperone binding in rat brain
Gallagher, I., Clow, A., Jenner, P. and Glover, V. 1999. Long term effects of pergolide and (-)-deprenyl on 3H-mazindol and 3H-spiperone binding in rat brain. Neurobiology of Aging. 20 (6), pp. 709-713. https://doi.org/10.1016/S0197-4580(99)00026-3

The awakening cortisol response and blood glucose levels
Hucklebridge, F., Clow, A., Abeyguneratne, T., Huezo-Diaz, P. and Evans, P. 1999. The awakening cortisol response and blood glucose levels. Life Sciences. 64 (11), pp. 931-937. https://doi.org/10.1016/S0024-3205(99)00019-3

Effect of long-term administration of pergolide and (-) -deprenyl on age related decline in Hole Board activity and antioxidant activity in rats
Gallagher, I., Clow, A., Jenner, P. and Glover, V. 1999. Effect of long-term administration of pergolide and (-) -deprenyl on age related decline in Hole Board activity and antioxidant activity in rats. Biogenic Amines. 15, pp. 379-393.

The relationship between salivary secretory immunoglobulin A and cortisol: neuroendocrine response to awakening and the diurnal cycle
Hucklebridge, F., Clow, A. and Evans, P. 1998. The relationship between salivary secretory immunoglobulin A and cortisol: neuroendocrine response to awakening and the diurnal cycle. International Journal of Psychophysiology. 31 (1), pp. 69-76. https://doi.org/10.1016/S0167-8760(98)00042-7

Mind-body influences on immunity: lateralised control, stress, individual differences, and prophylaxis
Gruzelier, J., Clow, A., Evans, P., Lazar, I. and Walker, L. 1998. Mind-body influences on immunity: lateralised control, stress, individual differences, and prophylaxis. Annals of the New York Academy of Sciences. 851, pp. 487-494. https://doi.org/10.1111/j.1749-6632.1998.tb09027.x

The relationship between circadian patterns of salivary cortisol and endogenous inhibitor of monoamine oxidase A
Hucklebridge, F., Sen, S., Evans, P. and Clow, A. 1998. The relationship between circadian patterns of salivary cortisol and endogenous inhibitor of monoamine oxidase A. Life Sciences. 62 (25), pp. 2321-2328. https://doi.org/10.1016/S0024-3205(98)00213-6

Secretory immunoglobulin A and cardiovascular responses to mental arithmetic and cold pressor
Willemsen, G., Ring, C., Evans, P. and Clow, A. 1998. Secretory immunoglobulin A and cardiovascular responses to mental arithmetic and cold pressor. Psychophysiology. 35 (3), pp. 252-259. https://doi.org/10.1111/1469-8986.3530252

Regional and molecular separation of the four bioactivities of ‘tribulin’
Hucklebridge, F., Doyle, A., Pang, F.Y., Adlard, M., Evans, P. and Clow, A. 1998. Regional and molecular separation of the four bioactivities of ‘tribulin’. Neuroscience Letters. 240 (1), pp. 29-32. https://doi.org/10.1016/S0304-3940(97)00916-6

The role and regulation of monoamines in stress
Clow, A., Hucklebridge, F. and Evans, P. 1998. The role and regulation of monoamines in stress. in: Levi, A., Grauer, E., Ben-Nathan, D. and de Kloet, E.R. (ed.) New frontiers in stress research: modulation of brain function Amsterdam Harwood Academic. pp. 21-31

The cortisol response to psychological challenge is preceded by a rise in endogenous inhibitor of monoamine oxidase.
Clow, A., Patel, S., Najafi, M., Evans, P. and Hucklebridge, F. 1997. The cortisol response to psychological challenge is preceded by a rise in endogenous inhibitor of monoamine oxidase. Life Sciences. 61 (5), pp. 567-575. https://doi.org/10.1016/S0024-3205(97)00416-5

Raised blood albumin levels are associated with trait anxiety
Stones, A., Groome, D.H., Clow, A. and Hucklebridge, F. 1997. Raised blood albumin levels are associated with trait anxiety. Depression & Anxiety. 4 (3), pp. 151-152. https://doi.org/10.1002/(SICI)1520-6394(1996)4:3<151::AID-DA10>3.0.CO;2-V

Long term administration of (-)-deprenyl increases mortality in male wistar rats
Gallagher, I., Clow, A. and Glover, V. 1997. Long term administration of (-)-deprenyl increases mortality in male wistar rats. Journal of Neural Transmission (supplement). 52, pp. 321-326.

Endogenous monoamine oxidase A inhibitory activity (tribulin), measured in saliva, is related to cardiovascular reactivity in normal individuals
Clow, A., Doyle, A., Hucklebridge, F., Carroll, D., Ring, C., Shrimpton, J., Willemsen, G. and Evans, P. 1997. Endogenous monoamine oxidase A inhibitory activity (tribulin), measured in saliva, is related to cardiovascular reactivity in normal individuals. Journal of Neural Transmission (supplement). 52, pp. 77-83.

Modulation of secretory immunoglobulin A in saliva in relation to an acute episode of stress and arousal
Bristow, M., Hucklebridge, F., Clow, A. and Evans, P. 1997. Modulation of secretory immunoglobulin A in saliva in relation to an acute episode of stress and arousal. Journal of Psychophysiology. 11 (3), pp. 248-255.

Positive but not negative life events predict vulnerability to upper respiratory illness
Evans, P., Doyle, A., Hucklebridge, F. and Clow, A. 1996. Positive but not negative life events predict vulnerability to upper respiratory illness. British Journal of Health Psychology. 1 (4), pp. 339-348. https://doi.org/10.1111/j.2044-8287.1996.tb00514.x

Salivary monoamine oxidase A and B inhibitory activities correlate with stress
Doyle, A., Hucklebridge, F., Evans, P. and Clow, A. 1996. Salivary monoamine oxidase A and B inhibitory activities correlate with stress. Life Sciences. 59 (16), pp. 1357-1362. https://doi.org/10.1016/0024-3205(96)00461-4

Isatin: a link between natriuretic peptides and monoamines?
Medvedev, A.E., Clow, A., Sandler, M. and Glover, V. 1996. Isatin: a link between natriuretic peptides and monoamines? Biochemical Pharmacology. 52 (3), pp. 385-391. https://doi.org/10.1016/0006-2952(96)00206-7

Urinary output of endogenous monoamine oxidase inhibitory activity is related to everyday stress
Doyle, A., Hucklebridge, F., Evans, P. and Clow, A. 1996. Urinary output of endogenous monoamine oxidase inhibitory activity is related to everyday stress. Life Sciences. 58 (20), pp. 1723-1730. https://doi.org/10.1016/0024-3205(96)00153-1

Tribulin and stress in normal individuals
Doyle, A., Pang, F.Y., Hucklebridge, F., Evans, P. and Clow, A. 1996. Tribulin and stress in normal individuals. in: McCarty, R., Aguilera, G., Sabban, E. and Kvetnansky, R. (ed.) Stress: molecular genetic and neurobiological advances Amsterdam Harwood Academic.

The relationship between isatin and monoamine oxidase-B inhibitory activity in urine
Pang, F.Y., Hucklebridge, F., Forster, G., Tan, K. and Clow, A. 1996. The relationship between isatin and monoamine oxidase-B inhibitory activity in urine. Stress Medicine. 12 (1), pp. 35-42. https://doi.org/10.1002/(SICI)1099-1700(199601)12:1<35::AID-SMI676>3.0.CO;2-2

Urinary cortisol and endogenous monoamine oxidase inhibitor(s), but not isatin, are raised in anticipation of stress and/or arousal in normal individuals
Doyle, A., Pang, F.Y., Bristow, M., Hucklebridge, F., Evans, P. and Clow, A. 1996. Urinary cortisol and endogenous monoamine oxidase inhibitor(s), but not isatin, are raised in anticipation of stress and/or arousal in normal individuals. Stress Medicine. 12 (1), pp. 43-49. https://doi.org/10.1002/(SICI)1099-1700(199601)12:1<43::AID-SMI677>3.0.CO;2-4

Effects of pergolide, (-)-deprenyl and thioridazine on soluble SOD, catalase and glutathione peroxidase in rat striata
Pattichis, K., Louca, L.L., Clow, A. and Glover, V. 1995. Effects of pergolide, (-)-deprenyl and thioridazine on soluble SOD, catalase and glutathione peroxidase in rat striata. Medical Science Research. 23, pp. 733-735.

Secretory immunoglobulin A as convenient biomarker in health survey work
Evans, P., Hucklebridge, F., Clow, A. and Doyle, A. 1995. Secretory immunoglobulin A as convenient biomarker in health survey work. in: Rodriguez-Martin, J. (ed.) Health psychology and quality of life research: Proceedings of the 8th Annual Conference of the European Health Psychology Society Alicante University of Alicante.

Stress, arousal, Cortisol and secretory immunoglobulin A in students undergoing assessment
Evans, P., Bristow, M., Hucklebridge, F., Clow, A. and Pang, F.Y. 1994. Stress, arousal, Cortisol and secretory immunoglobulin A in students undergoing assessment. British Journal of Clinical Psychology. 33 (4), pp. 575-576. https://doi.org/10.1111/j.2044-8260.1994.tb01154.x

Dysphoria and immune status in postpartum women
Hucklebridge, F., Smith, M.D., Clow, A., Evans, P., Glover, V., Taylor, A., Adams, D. and Lydyard, P.M. 1994. Dysphoria and immune status in postpartum women. Biological Psychology. 37 (3), pp. 199-206. https://doi.org/10.1016/0301-0511(94)90002-7

The effect of pergolide and MDL 72974 on rat brain CuZn superoxide dismutase
Clow, A., Freestone, C., Lewis, E., Dexter, D., Sandler, M. and Glover, V. 1993. The effect of pergolide and MDL 72974 on rat brain CuZn superoxide dismutase. Neuroscience Letters. 164 (1-2), pp. 41-43. https://doi.org/10.1016/0304-3940(93)90852-C

The relationship between secretory immunity, mood and life-events
Evans, P., Bristow, M., Hucklebridge, F., Clow, A. and Walters, N. 1993. The relationship between secretory immunity, mood and life-events. British Journal of Clinical Psychology. 32 (2), pp. 227-236. https://doi.org/10.1111/j.2044-8260.1993.tb01050.x

Effects of dopaminergic drugs on superoxide dismutase: implications for senescence
Glover, V., Clow, A. and Sandler, M. 1993. Effects of dopaminergic drugs on superoxide dismutase: implications for senescence. Journal of Neural Transmission (supplement). 40, pp. 37-45.

Changes in plasma cortisol and catecholamine concentrations in response to massage in preterm infants
Acolet, D., Modi, N., Giannakoulopoulos, X., Bond, C., Weg, W., Clow, A. and Glover, V. 1993. Changes in plasma cortisol and catecholamine concentrations in response to massage in preterm infants. Archives of Disease in Childhood. 68 (1), pp. 29-31. https://doi.org/10.1136/adc.68.1_Spec_No.29

Inhibitory potency of some isatin analogues on human monoamine oxidase A and B
Medvedev, A.E., Goodwin, B.L., Clow, A., Halket, J., Glover, V. and Sandler, M. 1992. Inhibitory potency of some isatin analogues on human monoamine oxidase A and B. Biochemical Pharmacology. 44 (3), pp. 590-592. https://doi.org/10.1016/0006-2952(92)90454-Q

Pergolide can induce soluble Superoxide dismutase in rat striata
Clow, A., Hussain, T., Glover, V., Sandler, M., Walker, M. and Dexter, D. 1992. Pergolide can induce soluble Superoxide dismutase in rat striata. Journal of Neural Transmission. 90 (1), pp. 27-31. https://doi.org/10.1007/BF01250515

Effect of aromatic amino acids, pentylenetetrazole and yohimbine on isatin and tribulin activity in rat brain
Bhattacharya, S.K., Clow, A., Przyborowska, A., Halket, J., Glover, V. and Sandler, M. 1991. Effect of aromatic amino acids, pentylenetetrazole and yohimbine on isatin and tribulin activity in rat brain. Neuroscience Letters. 132 (1), pp. 44-46. https://doi.org/10.1016/0304-3940(91)90429-W

(−)-Deprenyl can induce soluble superoxide dismutase in rat striata
Clow, A., Hussain, T., Glover, V., Sandler, M., Dexter, D. and Walker, M. 1991. (−)-Deprenyl can induce soluble superoxide dismutase in rat striata. Journal of Neural Transmission. 86 (1), pp. 77-80. https://doi.org/10.1007/BF01250378

Isatin (indole-2,3-dione) in urine and tissues: detection and determination by gas chromatography—mass spectrometry
Halket, J., Watkins, P.J., Przyborowska, A., Goodwin, B.L., Clow, A., Glover, V. and Sandler, M. 1991. Isatin (indole-2,3-dione) in urine and tissues: detection and determination by gas chromatography—mass spectrometry. Journal of Chromatography B: Biomedical Sciences and Applications. 562 (1-2), pp. 279-287. https://doi.org/10.1016/0378-4347(91)80585-Z

Isatin, regional distribution in rat brain and tissues
Watkins, P.J., Clow, A., Halket, J., Przyborowska, A. and Sandler, M. 1990. Isatin, regional distribution in rat brain and tissues. Neurochemistry International. 17 (2), pp. 321-323. https://doi.org/10.1016/0197-0186(90)90154-L

Stress reduces in vivo inhibition of monoamine oxidase by phenelzine in rat brain
Clow, A., Glover, V., Oxenkrug, G.F. and Sandler, M. 1989. Stress reduces in vivo inhibition of monoamine oxidase by phenelzine in rat brain. Neuroscience Letters. 107 (1-3), pp. 331-334. https://doi.org/10.1016/0304-3940(89)90841-0

Isatin and tribulin concentrations are increased in rabbit brain but not liver following pentylenetetrazole administration
Clow, A., Davidson, J., Glover, V., Halket, J., Milton, A.S., Sandler, M. and Watkins, P.J. 1989. Isatin and tribulin concentrations are increased in rabbit brain but not liver following pentylenetetrazole administration. Neuroscience Letters. 107 (1-3), pp. 327-330. https://doi.org/10.1016/0304-3940(89)90840-9

Tribulin: an endocoid marker for anxiety in man
Sandler, M., Clow, A., Watkins, P.J. and Glover, V. 1988. Tribulin: an endocoid marker for anxiety in man. Stress Medicine. 4 (4), pp. 215-219. https://doi.org/10.1002/smi.2460040406

Isatin: identity with the purified endogenous monoamine oxidase inhibitor tribulin
Glover, V., Halket, J., Watkins, P.J., Clow, A., Goodwin, B.L. and Sandler, M. 1988. Isatin: identity with the purified endogenous monoamine oxidase inhibitor tribulin. Journal of Neurochemistry. 51 (2), pp. 656-659. https://doi.org/10.1111/j.1471-4159.1988.tb01089.x

Tribulin in post-traumatic stress disorder
Davidson, J., Glover, V., Clow, A., Kudler, H., Meador, K. and Sandler, M. 1988. Tribulin in post-traumatic stress disorder. Psychological Medicine. 18 (4), pp. 833-836. https://doi.org/10.1017/S0033291700009764

Urinary catecholamine metabolite and tribulin output during lactate infusion
Clow, A., Glover, V., Weg, M.W., Walker, P.L., Sheehan, D.V., Carr, D.B. and Sandler, M. 1988. Urinary catecholamine metabolite and tribulin output during lactate infusion. British Journal of Psychiatry. 152, pp. 122-126. https://doi.org/10.1192/bjp.152.1.122

Increased urinary tribulin output in generalised anxiety disorder
Clow, A., Glover, V., Sandler, M. and Tiller, J. 1988. Increased urinary tribulin output in generalised anxiety disorder. Psychopharmacology. 95 (3), pp. 378-380. https://doi.org/10.1007/BF00181951

Tribulin output in neurological disorders
Clow, A., Glover, V., Sandler, M., Elwes, R. and Reynolds, E.H. 1987. Tribulin output in neurological disorders. British Journal of Clinical Pharmacology. 24 (3), pp. 403-404.

Purification and characterization of tribulin, an endogenous inhibitor of monoamine oxidase and of benzodiazepine receptor binding
Elsworth, J.D., Dewar, D., Glover, V., Goodwin, B.L., Clow, A. and Sandler, M. 1986. Purification and characterization of tribulin, an endogenous inhibitor of monoamine oxidase and of benzodiazepine receptor binding. Journal of Neural Transmission. 67 (1-2), pp. 45-56. https://doi.org/10.1007/BF01243358

Triazolam, an anomalous benzodiazepine receptor ligand: in vitro characterization of alprazolam and triazolam binding
Clow, A., Glover, V. and Sandler, M. 1985. Triazolam, an anomalous benzodiazepine receptor ligand: in vitro characterization of alprazolam and triazolam binding. Journal of Neurochemistry. 45 (2), pp. 621-625. https://doi.org/10.1111/j.1471-4159.1985.tb04031.x

Effects of discontinuous drug administration on the development of dopamine receptor supersensitivity during chronic trifluoperazine or cis-flupenthixol administration to rats
Murugaiah, K., Theodorou, A., Clow, A., Jenner, P. and Marsden, C.D. 1985. Effects of discontinuous drug administration on the development of dopamine receptor supersensitivity during chronic trifluoperazine or cis-flupenthixol administration to rats. Psychopharmacology. 86 (1-2), pp. 228-232. https://doi.org/10.1007/BF00431715

New endogenous benzodiazepine receptor ligand in human urine: identity with endogenous monoamine oxidase inhibitor?
Clow, A., Glover, V., Armando, I. and Sandler, M. 1983. New endogenous benzodiazepine receptor ligand in human urine: identity with endogenous monoamine oxidase inhibitor? Life Sciences. 33 (8), pp. 735-741. https://doi.org/10.1016/0024-3205(83)90778-6

Ethanol preference in rats: increased consumption after intraventricular administration of tetrahydropapaveroline
Clow, A., Stolerman, I.P., Murray, R.M. and Sandler, M. 1983. Ethanol preference in rats: increased consumption after intraventricular administration of tetrahydropapaveroline. Neuropharmacology. 22 (4), pp. 563-565. https://doi.org/10.1016/0028-3908(83)90181-8

Raised endogenous monoamine oxidase inhibitor output in postwithdrawal alcoholics: effects of L-dopa and ethanol.
Bhattacharya, S.K., Glover, V., Sandler, M., Clow, A., Topham, A., Bernadt, M. and Murray, R.M. 1982. Raised endogenous monoamine oxidase inhibitor output in postwithdrawal alcoholics: effects of L-dopa and ethanol. Biological Psychiatry. 17 (7).

Chronic continuous administration of neuroleptic drugs alters cerebral dopamine receptors and increases spontaneous dopaminergic action in the striatum
Murugaiah, K., Theodorou, A., Mann, S., Clow, A., Jenner, P. and Marsden, C.D. 1982. Chronic continuous administration of neuroleptic drugs alters cerebral dopamine receptors and increases spontaneous dopaminergic action in the striatum. Nature. 296, pp. 570-572. https://doi.org/10.1038/296570a0

Chronic neuroleptic treatment specifically alters the number of dopamine receptors in rat brain
Theodorou, A., Gommeren, W., Clow, A., Leysen, J., Jenner, P. and Marsden, C.D. 1981. Chronic neuroleptic treatment specifically alters the number of dopamine receptors in rat brain. Life Sciences. 28 (14), pp. 1621-1627. https://doi.org/10.1016/0024-3205(81)90317-9

Neuroleptic-induced acute dystonic reactions may be due to enhanced dopamine release on to supersensitive postsynaptic receptors
Kolbe, H., Clow, A., Jenner, P. and Marsden, C.D. 1981. Neuroleptic-induced acute dystonic reactions may be due to enhanced dopamine release on to supersensitive postsynaptic receptors. Neurology. 31 (4(2)), pp. 434-439.

During one year's neuroleptic treatment in rats, striatal dopamine receptor blockade decreases but serum prolactin levels remain elevated
Dyer, R.G., Murugaiah, K., Theodorou, A., Clow, A., Jenner, P. and Marsden, C.D. 1981. During one year's neuroleptic treatment in rats, striatal dopamine receptor blockade decreases but serum prolactin levels remain elevated. Life Sciences. 28 (2), pp. 167-174. https://doi.org/10.1016/0024-3205(81)90549-X

Stereoselective actions of substituted benzamide drugs on cerebral dopamine mechanisms
Jenner, P., Clow, A., Reavill, C., Theodorou, A. and Marsden, C.D. 1980. Stereoselective actions of substituted benzamide drugs on cerebral dopamine mechanisms. Journal of Pharmacy and Pharmacology. 32 (1), pp. 39-44. https://doi.org/10.1111/j.2042-7158.1980.tb12842.x

A comparison of striatal and mesolimbic dopamine function in the rat during 6-month trifluoperazine administration
Clow, A., Jenner, P., Theodorou, A. and Marsden, C.D. 1980. A comparison of striatal and mesolimbic dopamine function in the rat during 6-month trifluoperazine administration. Psychopharmacology. 69 (3), pp. 227-233. https://doi.org/10.1007/BF00433087

Changes in rat striatal dopamine turnover and receptor activity during one years neuroleptic administration
Clow, A., Theodorou, A., Jenner, P. and Marsden, C.D. 1980. Changes in rat striatal dopamine turnover and receptor activity during one years neuroleptic administration. European Journal of Pharmacology. 63 (2-3), pp. 135-144. https://doi.org/10.1016/0014-2999(80)90437-9

Cerebral dopamine function in rats following withdrawal from one year of continuous neuroleptic administration
Clow, A., Theodorou, A., Jenner, P. and Marsden, C.D. 1980. Cerebral dopamine function in rats following withdrawal from one year of continuous neuroleptic administration. European Journal of Pharmacology. 63 (2-3), pp. 145-157. https://doi.org/10.1016/0014-2999(80)90438-0

Antagonism by propanol of central dopamine receptor stimulation is not related to β-adrenergic blockade
Luscombe, G., Clow, A., Jenner, P. and Marsden, C.D. 1979. Antagonism by propanol of central dopamine receptor stimulation is not related to β-adrenergic blockade. Journal of Pharmacy and Pharmacology. 31 (1), pp. 355-356. https://doi.org/10.1111/j.2042-7158.1979.tb13522.x

Changes in dopamine-mediated behaviour during one year's neuroleptic administration
Clow, A., Jenner, P. and Marsden, C.D. 1979. Changes in dopamine-mediated behaviour during one year's neuroleptic administration. European Journal of Pharmacology. 57 (4), pp. 365-375. https://doi.org/10.1016/0014-2999(79)90499-0

Neuroleptic drugs and the dopamine hypothesis
Clow, A., Jenner, P., Theodorou, A. and Marsden, C.D. 1979. Neuroleptic drugs and the dopamine hypothesis. Lancet. 313 (8122), p. 934. https://doi.org/10.1016/S0140-6736(79)91424-7

Striatal dopamine receptors become supersensitive while rats are given trifluoperazine for six months
Clow, A., Jenner, P., Theodorou, A. and Marsden, C.D. 1979. Striatal dopamine receptors become supersensitive while rats are given trifluoperazine for six months. Nature. 278, pp. 59-61. https://doi.org/10.1038/278059a0

A comparison of in vitro and in vivo dopamine receptor antagonism produced by substituted benzamide drugs
Jenner, P., Elliott, P.N.C., Clow, A., Reavill, C. and Marsden, C.D. 1978. A comparison of in vitro and in vivo dopamine receptor antagonism produced by substituted benzamide drugs. Journal of Pharmacy and Pharmacology. 30 (1), pp. 46-48. https://doi.org/10.1111/j.2042-7158.1978.tb13151.x

A behavioural and biochemical comparison of dopamine receptor blockade produced by haloperidol with that produced by substituted benzamide drugs
Jenner, P., Clow, A., Reavill, C., Theodorou, A. and Marsden, C.D. 1978. A behavioural and biochemical comparison of dopamine receptor blockade produced by haloperidol with that produced by substituted benzamide drugs. Life Sciences. 23 (6), pp. 557-561. https://doi.org/10.1016/0024-3205(78)90032-2

An experimental model of tardive dyskinesias
Clow, A., Jenner, P., Theodorou, A. and Marsden, C.D. 1978. An experimental model of tardive dyskinesias. Life Sciences. 23 (5), pp. 421-423. https://doi.org/10.1016/0024-3205(78)90146-7

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