Long-term cognitive dysfunction in the rat following docetaxel treatment is ameliorated by the phosphodiesterase-4 inhibitor, rolipram.

Incidence of commonly experienced non-haematol...
Incidence of commonly experienced non-haematological adverse effects reported for treatment with docetaxel. Data from 40 phase II and phase III studies (n=2045) with patients undergoing a one-hour infusion of 100 mg/m 2 docetaxel once every three weeks. (Photo credit: Wikipedia)

Long-term cognitive dysfunction in the rat following docetaxel treatment is ameliorated by the phosphodiesterase-4 inhibitor, rolipram.

Our latest paper [download] focuses on chemobrain – the mental fog or fuzziness that can accompany and follow chemotherapy.

Behav Brain Res. 2015 May 1;290:84-89. doi: 10.1016/j.bbr.2015.04.044. [Epub ahead of print]

Callaghan CK, O’Mara SM.

Clinical studies report evidence of long-term cognitive and other deficits following adjunctive chemotherapy treatment, which is often termed “chemobrain” or “chemo-fog“. The neurological bases of these impairments are poorly understood. Here, we hypothesize that systemic chemotherapy treatment causes long-term neurobehavioral deficits, and that these deficits are reversed by manipulation of cAMP by the PDE4 inhibitor, rolipram. Male han Wistar rats were treated with docetaxel (an adjunctive chemotherapeutic agent (1mg/kg i.v.)) or control solution (ethanol/Tween 20/0.9% Saline – 5/5/90) once per week for 4 weeks. They were allowed to recover for 4 weeks, administration of rolipram (0.5mg/kg po) or vehicle (maple syrup) then began and continued daily for 4 weeks. At the end of the treatment regime animals were tested for spatial and recognition memory deficits with the object exploration task and for depressive- and anxiety-like behavior in the forced swim test (FST) and open field exploration. We report docetaxel treatment impaired spatial memory but not object recognition memory, compared to control rats. Docetaxel-treated rats also spent significantly more time immobile than controls in the FST. Chronic rolipram treatment attenuated all of these docetaxel-associated changes, recovering spatial memory and reducing immobility. In conclusion, docetaxel-treated rats exhibit alterations in spatial memory and depressive-like behavior, which are reversed following chronic rolipram administration. These results detect long-term cognitive and mood changes following docetaxel treatment and identify PDE4 inhibition as a target treatment of neuropsychological changes associated with “chemobrain”.
Copyright © 2015 Elsevier B.V. All rights reserved.

KEYWORDS:
Chemobrain; Chemotherapy; Cognition; Docetaxel; Mood; cAMP

[PS: My book Why Torture Doesn’t Work: The Neuroscience of Interrogation’ (Harvard UP) which also deals with, among other things, interrogating the memory systems of the brain under duress, can be preordered from Amazon (.com)]

Author: Shane O'Mara

Neuroscientist

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