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Chapter 10. Neurobiology of Stimulants

Margaret Haney, Ph.D.
DOI: 10.1176/appi.books.9781585623440.346622

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Cycles of amphetamine and cocaine abuse have occurred throughout the world for more than a century. In the United States, use of methamphetamine, which is the primary type of amphetamine abused, has dramatically increased. The number of admissions for methamphetamine treatment increased nearly fourfold from 1994 to 2004. In many areas of the country, the number of patients enrolled for methamphetamine treatment surpasses the number of patients in treatment for cocaine and heroin. Cocaine also remains a major public health issue, based on arrest statistics and drug treatment records. In fact, emergency room visits related to cocaine use increased by more than 22% between 1994 and 2001 (Office of National Drug Control Policy 2001; Substance Abuse and Mental Health Services Administration 2006a, 2006b).

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Table Reference Number
TABLE 10–1. Primary role of dopamine in stimulant reinforcement
Table Reference Number

The robust reinforcing properties of cocaine and methamphetamine are primarily mediated by their effects on dopamine in the ventral tegmental area, nucleus accumbens, ventral pallidum, and prefrontal cortex.

Cocaine and methamphetamine share similar subjective and reinforcing effects, yet important distinctions exist between these two stimulant drugs. Cocaine's effects are relatively short-lasting, resulting in a pattern of more frequent self-administration over a shorter period of time compared with methamphetamine. Furthermore, cocaine inhibits the reuptake of dopamine, whereas methamphetamine also promotes dopamine release, which renders this drug more neurotoxic than cocaine.

Chronic use of cocaine and methamphetamine produces long-term neuroadaptations that can increase the probability that people will choose to seek and use drug over other behaviors. A number of factors contribute to this shift in behavior:

1) Exposure to the cues associated with drug use may produce a strong desire to use the drug; stressful stimuli or a lapse to drug use also increases the desire to return to drug use.

2) Chronic stimulant use may alter the prefrontal brain circuits mediating decision making, thereby increasing the likelihood people will choose short-term immediate reinforcers (e.g., smoking methamphetamine) over long-term reinforcers (e.g., working steadily to receive a paycheck). In fact, impaired decision making appears to predict relapse.

Repeated stimulant-induced increases in extracellular dopamine and glutamate play a critical role in the cascade of events that lead to addiction, including changes in gene expression and synaptic plasticity.

Because of the intricate interactions between dopamine and other neurotransmitters, cocaine and amphetamine use may be modulated by medications acting on a range of neurochemical sites, particularly those modulating glutamate and -aminobutyric acid.

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