Info

Serotonin (5-hydroxytryptamine)

Psilocybin (mushrooms)

CH3 O

/CH3

XCH,

Dimethyltryptamine (DMT)

Psilocybin (mushrooms)

Dimethyltryptamine (DMT)

Psilocybin Next Nephrine

FIGURE 13-13

Molecular similarities between neurotransmitters (orange) and some euphorigens. At high doses, these euphorigens can cause hallucinations.

CH3 O

FIGURE 13-13

Molecular similarities between neurotransmitters (orange) and some euphorigens. At high doses, these euphorigens can cause hallucinations.

dopamine, serotonin, (Figure 13-13), and norepi-nephrine, and they interact with the receptors activated by these transmitters.

Dependence Substance dependence, the term now preferred for addiction, has two facets that may occur either together or independently: (1) a psychological dependence that is experienced as a craving for a substance and an inability to stop using the substance at will; and (2) a physical dependence that requires one to take the substance to avoid withdrawal, which is the spectrum of unpleasant physiological symptoms that occurs with cessation of substance use. Substance dependence is diagnosed if three or more of the characteristics listed in Table 13-3 occur within a 12-month period. Table 13-4 lists the dependence-producing potential of various drugs.

Several neuronal systems are involved in substance dependence, but most psychoactive substances act on the mesolimbic dopamine pathway (Figure 13-14). In addition to the actions of this system mentioned earlier in the context of motivation and emotion, the mesolim-bic dopamine pathway allows a person to experience pleasure in response to pleasurable events or in response to certain substances. Although the major neu-rotransmitter implicated in addiction is dopamine, other neurotransmitters, including GABA, enkephalin, serotonin, and glutamate, are also involved.

According to popular opinion, people use substances primarily to feel pleasure, but some researchers are presenting a different view. They believe that in people who become substance dependent, the neuro-transmitters may be handled abnormally in the mesolimbic dopamine pathway due in part to a genetic

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

Consciousness and Behavior CHAPTER THIRTEEN

Consciousness and Behavior CHAPTER THIRTEEN

TABLE 13-3 Diagnostic Criteria for Substance Dependence

TABLE 13-4 Potential of Various Substances to Cause Dependence

Substance dependence is indicated when three or more of the following occur within a 12-month period.

1. Tolerance, as indicated by a. a need for increasing amounts of the substance to achieve the desired effect, or b. decreasing effects when continuing to use the same amount of the substance

2. Withdrawal, as indicated by a. appearance of the characteristic withdrawal symptoms upon stopping use of the substance, or b. use of the substance (or one closely related to it) to relieve or avoid withdrawal symptoms

3. Use of the substance in larger amounts or for longer periods of time than intended

4. Persistent desire for the substance; unsuccessful attempts to cut down or control use of the substance

5. A great deal of time is spent in activities necessary to obtain the substance, use it, or recover from its effects

6. Occupational, social, or recreational activities are given up or reduced because of substance use

7. Use of the substance is continued despite knowledge that one has a physical or psychological problem that is likely to be exacerbated by the substance

Adapted from DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association, Washington, D.C., 1994.

alteration. Thus, by using substances, addicts are self-medicating in an attempt to stabilize the activity in this pathway so they can feel normal and relaxed. In other cases, people use substances primarily to avoid the discomfort of withdrawal.

Tolerance Tolerance to a substance occurs when increasing doses of the substance are required to achieve effects that initially occurred in response to a smaller dose; that is, it takes more of the substance to do the same job. Moreover, tolerance can develop to one substance as a result of taking another substance, in which case, it is called cross-tolerance. Substance tolerance and cross-tolerance can occur with many classes of substances and are not limited to psychoactive substances.

Tolerance may develop because the presence of the substance stimulates the synthesis, especially in the microsomal enzyme system (Chapter 20), of the enzymes that degrade it. As substance concentrations increase, so do the concentrations of the enzymes that degrade it. Thus, more of the substance must be administered to produce the same plasma concentrations of the substance and hence the same initial effect.

TABLE 13-4 Potential of Various Substances to Cause Dependence

If 100 people use a substance, how many will become dependent on it?

Nicotine

33

Heroin

25

Cocaine

16

Alcohol

15

Amphetamines

1111

Marijuana

People Who Use Barbiturates
Barbiturates? Benzodiazepines?

FIGURE 13-14

The sites at which various psychoactive substances are thought to work by enhancing brain reward. The mesolimbic dopamine pathway is indicated schematically by the red neurons. THC = tetrahydrocannabinol, the active ingredient in marijuana.

Nucleus accumbens —

Amphetamine Cocaine Opiates THC

Phencyclidine Midbrain nuclei

Keta)mine "opaes-

Nicotine Ethanol?

Barbiturates? Benzodiazepines?

Barbiturates? Benzodiazepines?

FIGURE 13-14

The sites at which various psychoactive substances are thought to work by enhancing brain reward. The mesolimbic dopamine pathway is indicated schematically by the red neurons. THC = tetrahydrocannabinol, the active ingredient in marijuana.

Alternatively, tolerance can develop as a result of changes in the number and/or sensitivity of receptors that respond to the substance, the amount or activity of enzymes involved in neurotransmitter synthesis, the reuptake transport molecules, or the signal transduc-tion pathways in the postsynaptic cell.

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