Chemotherapy-induced
cognitive impairment, known also as “chemobrain”,
is a medical complication of cancer treatment that is characterized
by a general decline in cognition affecting visual and verbal memory,
attention, complex problem solving skills, and motor function. It
is estimated that one-third of patients who undergo chemotherapy treatment
will experience cognitive impairment. Alterations in the release and
uptake of dopamine and serotonin, central nervous system neurotransmitters
that play important roles in cognition, could potentially contribute
to impaired intellectual performance in those impacted by chemobrain.
To investigate how chemotherapy treatment affects these systems, fast-scan
cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used
to measure dopamine and serotonin release and uptake in coronal brain
slices containing the striatum and dorsal raphe nucleus, respectively.
Measurements were taken from rats treated weekly with selected doses
of carboplatin and from control rats treated with saline. Modeling
the stimulated dopamine release plots revealed an impairment of dopamine
release per stimulus pulse (80% of saline control at 5 mg/kg and 58%
at 20 mg/kg) after 4 weeks of carboplatin treatment. Moreover, Vmax, the maximum uptake rate of dopamine, was
also decreased (55% of saline control at 5 mg/kg and 57% at 20 mg/kg).
Nevertheless, overall dopamine content, measured in striatal brain
lysates by high performance liquid chromatography, and reserve pool
dopamine, measured by FSCV after pharmacological manipulation, did
not significantly change, suggesting that chemotherapy treatment selectively
impairs the dopamine release and uptake processes. Similarly, serotonin
release upon electrical stimulation was impaired (45% of saline control
at 20 mg/kg). Measurements of spatial learning discrimination were
taken throughout the treatment period and carboplatin was found to
alter cognition. These studies support the need for additional neurochemical
and behavioral analyses to identify the underlying mechanisms of chemotherapy-induced
cognitive disorders.