Induced sickness symptoms change the behaviour of a rat. ©Huw Jones/Alamy stock photo

Induced sickness symptoms change the behaviour of a rat. ©Huw Jones/Alamy stock photo

What impact do negative experiences have on the potential side effects of a treatment?

Patients undergoing immunotherapy or chemotherapy often develop symptoms such as anxiety, depression or fatigue as side effects. These become more intense the longer the treatment lasts, and can be induced simply by entering the hospital, even before the medication is administered. How exactly is this learned development of symptoms triggered by negative treatment expectations? This project uses an animal model to investigate the neurobiological mechanisms, with the long-term objective of improving the efficiency and tolerability of treatments.

Neurobiological mechanisms of negative treatment expectations in an animal model for endotoxin-induced sickness behaviour

This project investigates the neurobiological mechanisms of negative expectation effects in an animal model for learned sickness behaviour. The effects of a previous negative treatment experience on the intensity of sickness symptoms will be analysed at behavioural, physiological and neural level. The particular importance of the central fear network and insula for the initiation and maintenance of negative expectation effects will be investigated through chemogenetic inhibition of neural activity in these areas of the brain.

Recommended reading:

Doenlen R, Krügel U, Wirth T, Riether C, Engler A, Prager G, Engler H, Schedlowski M, Pacheco-López G (2011) Electrical activity in rat corticolimbic structures after single or repeated administration of lipopolysaccharide or staphylococcal enterotoxin B. Proc Royal Soc B Biol Sci 278: 1864-1872. PubMed

Engler H, Brendt P, Wischermann J, Wegner A, Röhling R, Schoemberg T, Meyer U, Gold R, Peters J, Benson S, Schedlowski M (2017) Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms. Mol Psychiatry 22: 1448-1454. PubMed

Prager G, Hadamitzky M, Engler A, Doenlen R, Wirth T, Pacheco-Lopez G, Krugel U, Schedlowski M, Engler H (2013) Amygdaloid signature of peripheral immune activation by bacterial lipopolysaccharide or staphylococcal enterotoxin B. J Neuroimmune Pharmacol 8: 42-50. PubMed

In close cooperation with these projects

A01

A01

A02

A02

A03

A03

A04

A04

A09

A09

How is the effect of antidepressants influenced by treatment experiences?

Prof. Dr. Markus Wöhr
Prof. Dr. Rainer K.W. Schwarting

A11

A11

Project Lead

Prof. Dr. Harald Engler

Prof. Dr. Harald Engler
Biologist

Dr. Laura Heiß-Lückemann
Biologist

Team

Kirsten Dombrowski
Postdoc, Biologist