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Cocaine is one of the oldest stimulants known to humans. Originally used by the Incas to facilitate physical activity at high altitudes, thanks to its ability to increase breathing and heart rate. Its popularity took off in the 1880s when physicians (led by Sigmund Freud) promoted it as a wonder-drug, but its adverse addictive and physical effects promptly made it an illegal substance in 1914.

Cocaine is commonly snorted into the nasal cavity. Here, the drug diffuses into capillaries, through the endothelial layer, and past the blood-brain barrier. Cocaine affects a decision-making area of the brain called the Prefrontal Cortex, whose neural activity increases shortly after cocaine use. This hyperactivity is relayed to the sub-cortical reward system center which includes the Nucleus Accumbens and Dorsal Striatum. So cocaine hijacks the Prefrontal Cortex’s control over parts of the brain that allow individuals the ability to assess and differentiate between conflicting signals as well initiate the reward pathway. The Nucleus Accumbens and Dorsal Striatum collectively regulate reinforcement and behavior through innervation of the Ventral Tegmental Area (VTA) and Substantia Nigra (SNc). These areas of the brain are responsible for secreting dopamine, a neurotransmitter vital for reinforcing behavior in the dorsal striatum.

Neural activity is transmitted between neurons at points of contact called synapses. Here, electrical activity from one neuron is transformed into a chemical signal via the release of neurotransmitters, like dopamine, in neurons carrying reward signals. Cocaine interferes with the normal functioning of the brain by inhibiting dopamine reuptake. The drug blocks dopamine reuptake transporters leading to an accumulation of dopamine in the synapse, thus further stimulating the postsynaptic neuron. 

While cocaine is affecting the reward pathway, it simultaneously affects motor movement. Stimulation from the Nucleus Accumbens innervates the parts of the brain responsible for voluntary motor movement, the Ventral and Dorsal Globus Pallidus. The Nucleus Accumbens also has a direct effect on the Dorsal Striatum. Action potentials from the Dorsal Striatum are ultimately directed to the thalamus, which relays information to other parts of the brain and mediates motor control.

Cocaine addicts experience cravings when they have not used the drug for a period of time. This is because expectation alone, and drug-related cues, can mimic the effects of cocaine on PFC activation in addicted individuals. The craving sensation is a psychological urge that makes it difficult for many users to overcome their addiction. This phenomenon also primes the brain for a stronger response to drug use while reinforcing the drug-using behavior. 

The Amygdala, highlighted as a purple sphere and the Hippocampus, highlighted as the pink curved structure next to the Amygdala, are two main structures that drive the craving sensation. The amygdala responds to conditional cues from the environment such as the sight of the drug, while the Hippocampus is responsible for contextual cues from memory such as remembering the high associated with cocaine. Together, these two structures, along with the Prefrontal Cortex innervate the Nucleus Accumbens. The Nucleus Accumbens is important to the cocaine high as it is responsible for producing the feelings of pleasure and satisfaction.

Output from the Nucleus Accumbens goes to the dorsal striatum, where it feeds into the Thalamus and eventually to the dopamine-producing VTA and Substantia Nigra. Ultimately, dysfunction of the PFC leads to craving, compulsive drug use, and denial of addiction. The result is substance use disorder and rejection to treatment. Current efforts to address these concerns include the use of biomarkers in adolescents and children to identify at-risk individuals who may be prone to addiction. Medications also exist to help addicted individuals in rehabilitation activities.


Cocaine; Drug; Addiction; Dopamine; Reward pathway; Ventral Tegmental Area; Substantia Nigra; Prefrontal Cortex; Dorsal Striatum; Nucleus Accumbens; Amygdala; Globus Pallidus; Hippocampus








Advait Apte, Anna Cahn, Ching-Jung Chen, Katie Cheng, Timmy Eng, Lenn Hypolite, Rafay Malik, Hysell Oviedo


The City College Libraries, New York, New York






Cocaine Addiction Effects of the Brain: Binge and Craving by City College of New York Digital Scholarship Services is licensed under a Creative Commons Attribution 4.0 International License.
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