Use of Cocaine and the Central Nervous System

8/3/2019 Use of Cocaine and the Central Nervous System

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Cocaine, a psychostimulant of the central nervous system, has increased in

worldwide consumption (Alvarenga et. al., 2009) although its effects on the body

after repeated use can be drastic. Its effects on certain neurotransmitters, brain

structure, and neurological function can be permanent, and some of these changes

may add to its addictive potential. A better understanding of cocaines neurological

effects may lead to more effective rehabilitation methods, as well as preventative

measures for combating recreational cocaine abuse.

Cocaine produces its effects by blocking monoamine transporters and

impairing monoamine receptor signaling within the brain (Kubrusly & Bhide, 2009).

It also impairs dopamine receptor signaling as well as adenosine receptor signaling

(Kubrusly & Bhide, 2009). In a studying using cocaine dependent subjects as

diagnosed by DSM-IV criteria, Little et al estimated that cocaine use decreases the

total number of melanized dopamine cells in the anterior midbrain by

approximately 16% (Little et al., 2008). According to Daws et al., this is an indirect

effect of cocaine increasing dopamine transporter cellular location within cells,

which increases [3H]WIN 35428 binding (Little et al., 2008). Little et al.s study

showed an inverse correlation between total numbers of dopamine cells and striatal

[3H]WIN 35428 binding (Little et al., 2008). Because dopamine plays an important

role in the brain in governing behavior, motivation, and reward, a loss of dopamine

cells could contribute to or intensify cocaine dependence (Little et al., 2008). These

findings have important clinical implications in understanding the addictive

properties of cocaine and treating withdrawal. Cornelius et al. found that cocaine

users with withdrawal depression respond poorly to fluoxetine, a common anti-


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depressant, which may be because cocaine related mood disorders have causes

distinct from other affective disorders (Little et al., 2008). According to

Moszczynska et al., withdrawal related depression is better treated with

amantadine, a dopamine transport inhibitor (Little et al., 2008). Based on these

studies, it appears that using substances that increase dopamine levels in the brain

can more effectively treat cocaine addiction.

Cocaines effects on dopamine and other neurotransmitters are not restricted

to fully matured brains. Studies on cocaine exposure to the fetal brain in pregnant

mice during the first trimester of gestation have shown that cocaine reduces

dopamine uptake in the striatum of the embryos and downregulates adenosine

transporter function (Kubrusly & Bhide, 2009). In addition, dopamine D1-receptor

function is significantly impaired in cocaine-exposed embryonic striatum and

cerebral cortex. However, cocaine-exposed embryos showed significant increases in

dopamine D2-receptor activity in the striatum (Kubrusly & Bhide, 2009). Ohtani et

al and Popolo et al have concluded that dopamine D1- and D2-receptors generate

opposite effects on developmental events, such as neurogenesis (Kubrusly & Bhide,

2009). Fetal cocaine exposure influences dopamines physiological effects in favor

of the D2-receptor, which may lead to birth defects. Cocaine has also been shown to

inhibit growth of the neocortex when exposure is during the early and middle

periods of neurogenesis (Lee, Chen, Worden, & Freed, 2010). The same study found

that cocaine also changes the distribution of glutamate-positive cells in the

neocortex by increasing the number of glutamate-positive cells in ventricular zone

while decreasing the number of these cells in the cortical laminae. Further still, Lee


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et al. found that cocaine interrupts the tangential migration of GABA from the

ganglionic eminences to the neocortex, which causes an accumulation of GABA in

the subcortical telencephalon. Altered distribution of glutamate-positive cells and

GABA has been shown to cause problems in the neurochemical environment and in

cortical organization (Lee et al., 2008). Such findings should be made aware to

pregnant mothers with a history of cocaine use to prevent detrimental effects to

their offspring.

Cocaine addiction may also stem from an increase in brain activity associated

with its use (Henry, Murnane, Votaw, & Howell, 2010). Henry et al. conducted a

study on cocaine-induced changes in brain metabolic activity and discovered that

nave use results in increases in metabolism localized to the medial prefrontal

cortex, while extended use results in increased metabolic activity throughout the

entire prefrontal cortex and the striatum. By examining the extent of metabolic

effects in cocaine addicts, addiction treatment specialists will be better able to

understand the severity of ones drug dependence, giving indications for the need of

aggressive treatment approaches when metabolic activity has been greatly

increased (Henry et al., 2010).

While cocaine may increase metabolism in the prefrontal cortex, at the same

time it decreases its function and can cause cognitive deficits as well as DNA

damage. (Hampson, et al., 2010). Hampson et al. found that cocaine use may disrupt

performance of a cognitive task by altering neural processing in the prefrontal

cortex and decreasing brain glucose utilization rates. Cocaine has also been shown

to significantly lower gray matter volumes in the bilateral premotor cotex, the right


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orbitofrontal cotex, the bilateral temporal cortex, left thalamus, and the bilateral

cerebellum, as well as lower white matter volume in the right cerebellum (Sim et al.,

2006). According to Sim et al., lower gray and white matter volumes in the

cerebellum have been associated with deficits in executive function and motor

performance. Concentrations of nerve growth factor, an important component in

the survival and function of cholinergic neurons, is also lowered by prolonged

cocaine use (Angelucci et al., 2007). Since NGF regulates neuronal survival, a

reduction of its production can have detrimental effects on CNS neurons. This may

explain cognitive deficits such as reduced memory performance, decreased

attention span, and learning impairments (Angelucci et al., 2007) There is also

evidence that cocaine damages blood cell, liver, and brain DNA after a single dose,

potentially altering cell reproduction (Alvarenga et al., 2009). Cocaine can even

cause cell death in cortical neurons due to DNA fragmentation (Nassogne, Louahed,

Evrard, & Cortoy, 1997) The findings of Alvarenga et al and Nassogne et al conclude

that cocaine is a potent genotoxin in multiple organs.

Cocaine, one of the most addictive illicit drugs in use today (Alvarenga et al.,

2009), has been show to decrease natural dopamine levels in the brain, increase

metabolism in the prefrontal cortex, inflict DNA damage in a number of organs, and

causes cognitive deficits. The results of its mechanisms greatly add to its addictive

potential. Use by pregnant women can even result in birth defects in their offspring.

Research has been able to improve addiction treatment methods, and further

research on cocaine can uncover additional damaging effects of its usepotentially

deterring abuse.


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References

Alvarenga, T. A., Andersen, M. L., Ribeiro, D. A., Araujo, P., Hirotsu, C., Costa, J. L., &

... Tufik, S. (2010). Single exposure to cocaine or ecstasy induces DNA damage

in brain and other organs of mice.Addiction Biology, 15(1), 96-99.

doi:10.1111/j.1369-1600.2009.00179.x.

Hampson, R. E., Porrino, L. J., Opris, I., Stanford, T., & Deadwyler, S. A. (2011). Effects

of cocaine rewards on neural representations of cognitive demand in

nonhuman primates. Psychopharmacology, 213(1), 105-118.

doi:10.1007/s00213-010-2017-2.

Henry, P. K., Murnane, K. S., Votaw, J. R., & Howell, L. L. (2010, December). Acute

brain metabolic effects of cocaine in rhesus monkeys with a history of

cocaine use. Brain Imaging and Behavior, 4(3-4), 212-219.

doi:10.1007/s11682-010-9100-5.

Kubrusly, R. C., & Bhide, P. G. (2010). Cocaine exposure modulates dopamine and

adenosine signaling in the fetal brain. Neuropharmacology, 58(2), 436-443.

doi:10.1016/j.neuropharm.2009.09.007.

Lee, C., Chen, J., Worden, L. T., & Freed, W. J. (2011). Cocaine causes deficits in radial

migration and alters the distribution of glutamate and GABA neurons in the

developing rat cerebral cortex. Synapse, 65(1), 21-34.

doi:10.1002/syn.20814.

Lee, C., Lehrmann, E., Hayashi, T., Amable, R., Tsai, S., Chen, J., & ... Freed, W. J.

(2009). Gene expression profiling reveals distinct cocaine-responsive genes


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in human fetal CNS cell types. Journal of Addiction Medicine, 3(4), 218-226.

doi:10.1097/ADM.0b013e318199d863

Little, K. Y., Ramssen, E., Welchko, R., Volberg, V., Roland, C. J., & Cassin, B. (2009).

Decreased brain dopamine cell numbers in human cocaine users. Psychiatry

Research, 168(3), 173-180. doi:10.1016/j.psychres.2008.10.034. Cocaine use

causes a loss of dopamine neurons.

Narayana, P. A., Datta, S., Tao, G., Steinberg, J. L., & Moeller, F. (2010). Effect of

cocaine on structural changes in brain: MRI volumetry using tensor-based

morphometry. Drug and Alcohol Dependence, 111(3), 191-199.

doi:10.1016/j.drugalcdep.2010.04.012.

Nassogne, M.-C., Louahed, J., Evrard, P. and Courtoy, P. J. (1997), Cocaine induces

apoptosis in cortical neurons of fetal mice.Journal of Neurochemistry, 68:

2442- 2450. doi: 10.1046/j.1471-4159.1997.68062442.x

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Use of Cocaine and the Central Nervous System

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