23.20–23.22: Drugs can hijack the pleasure pathways.

The French poet Jacques Prévert tinkers with synaptic activity in his brain in Paris, 1955.

Stimulation of the reward centers in the brain spurs animals to behave in certain ways. We’re built this way on purpose: when we behave in ways important to our evolutionary fitness, our brain releases neurotransmitters such as dopamine. Exposed to such neurotransmitters, our pleasure centers produce the sensation of bliss. And that bliss spurs us to seek out that feeling again once it fades. Usually this system works well.

Our brain’s signaling system can be tricked, however, and with potentially disastrous consequences. Drugs—whether recreational or therapeutic, whether found in nature or made in the laboratory—can work by mimicking neurotransmitters. When we take a pleasure-causing drug, our brain experiences the same sensations as if appropriately released neurotransmitters were flooding the system. The brain cannot distinguish this artificial high from a natural high. There are several different methods by which drugs can influence our nervous system.

Cocaine When someone snorts a bit of cocaine, it crosses the blood-brain barrier and quickly reaches the brain’s pleasure centers. Once there, the cocaine binds to the sites on the presynaptic membrane where dopamine is normally reabsorbed from the synaptic cleft by the cells that originally released it. As long as these reuptake sites are blocked by the drug, dopamine released by that neuron remains in the synaptic cleft, repeatedly stimulating the postsynaptic cell and causing nonstop activity in the pleasure center (FIGURE 23-47).

Figure 23.47: Prolonging pleasure sensations.

Prozac and Zoloft Antidepressants work by a mechanism almost identical to that of cocaine. In addition to dopamine, another neurotransmitter important in our brain’s pleasure centers is serotonin. The antidepressants Prozac and Zoloft block serotonin from being reabsorbed and recycled by the presynaptic cells that released it, prolonging its effect (see Figure 23-47). This is why these drugs are called selective serotonin reuptake inhibitors (SSRIs). The net result is that people taking these medications generally experience an elevated mood because of serotonin’s prolonged stay in the synaptic cleft.

Morphine and Heroin Some chemical messengers we ought to be especially thankful for are the endorphins, our body’s natural painkillers. Produced by our brain, endorphins block pain messages arriving from throughout the body. Under a variety of situations of extreme stress—such as if an individual has just been seriously injured in a fight or is in mile 12 of a half-marathon—the body responds by releasing endorphins.

The popular opiates morphine and heroin mimic endorphins and bind to their receptor sites. With a large enough dose, opiate users can give themselves an “endorphin rush” and feelings of euphoria far more intense than anything possible with their own natural supply of these pleasure compounds. The respiratory slowdown that comes with heroin use can occur quickly and, with large doses of heroin, can be fatal.

Nicotine One of the most commonly used drugs is nicotine. Shortly after entering the bloodstream, nicotine begins mimicking one of the body’s most common and important neurotransmitters: acetylcholine. Fooled by the nicotine binding to acetylcholine receptors, cells release adrenaline and other stimulating chemicals, including pleasure-causing dopamine. Nicotine causes rapid surges, then rapid depletions, of these chemicals, leaving smokers happy for a short while but soon yearning for another cigarette.

When we consume drugs such as those described above, our bodies soon respond to the perception that there are larger amounts than usual of certain neurotransmitters. Usually the response is a reduction in sensitivity to the drug. Although tolerance is inevitable, its magnitude and consequences vary with the type of drug. In one study, volunteers were injected with a uniform daily dose of heroin and monitored for their level of euphoria. Initially they were ecstatic, but their bodies reacted by reducing the number of receptors that bind heroin. With fewer and fewer receptors, the euphoric heroin effects dropped almost to zero in just three weeks. Similar changes occur in response to using caffeine, nicotine, or alcohol.

Do human drug addictions and dependencies reflect differences in our genes? Recent data suggest that they might at least be influenced by the alleles a person carries. In one study of 283 individuals, a third of the people who smoked had a version (i.e., an allele) of an important gene that almost none of the non-smokers carried. This gene, labeled DRD4, codes for the receptor that enables the pleasure centers of our brain to respond to dopamine. The allele of the DRD4 gene implicated in this study of drug dependency was the same one we discussed in the StreetBio at the end of Chapter 7, a gene that appears to influence a variety of personality traits associated with risk-taking and novelty-seeking behavior (FIGURE 23-48).

Figure 23.48: Can a gene nudge you toward risk-taking?

In the next section we look at a popular and effective drug that acts, not by blocking neurotransmitter reuptake, but rather by blocking the postsynaptic receptors.