3 research outputs found
Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carbotplatin
Chemotherapy-induced cognitive impairment, known also as āchemobrainā, 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
Localized Drug Application and Sub-Second Voltammetric Dopamine Release Measurements in a Brain Slice Perfusion Device
The
use of fast scan cyclic voltammetry (FSCV) to measure the release
and uptake of dopamine (DA) as well as other biogenic molecules in
viable brain tissue slices has gained popularity over the last 2 decades.
Brain slices have the advantage of maintaining the functional three-dimensional
architecture of the neuronal network while also allowing researchers
to obtain multiple sets of measurements from a single animal. In this
work, we describe a simple, easy-to-fabricate perfusion device designed
to focally deliver pharmacological agents to brain slices. The device
incorporates a microfluidic channel that runs under the perfusion
bath and a microcapillary that supplies fluid from this channel up
to the slice. We measured electrically evoked DA release in brain
slices before and after the administration of two dopaminergic stimulants,
cocaine and GBR-12909. Measurements were collected at two locations,
one directly over and the other 500 Ī¼m away from the capillary
opening. Using this approach, the controlled delivery of drugs to
a confined region of the brain slice and the application of this chamber
to FSCV measurements, were demonstrated. Moreover, the consumption
of drugs was reduced to tens of microliters, which is thousands of
times less than traditional perfusion methods. We expect that this
simply fabricated device will be useful in providing spatially resolved
delivery of drugs with minimum consumption for voltammetric and electrophysiological
studies of a variety of biological tissues both in vitro and ex vivo