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Tiny squirrel monkeys are the latest warriors in the battle against cocaine abuse. Researchers at the Yerkes Regional Primate Research Center at Emory University are using the pint-sized primates to evaluate the potential of two drugs, quipazine and alaproclate, to act as treatments for cocaine addiction in humans. Currently, no effective treatment exists to help recovering addicts avoid using cocaine. A compound that would reduce or eliminate the pleasurable effects of cocaine, as it is believed quipazine and alaproclate might, would be a great boon to the treatment process.
Cocaine abuse remains one of the most intractable drug problems facing this nation, where close to 2 million people use cocaine at least once a month. Perhaps the most troubling statistics are for the 18 to 25-year-old age group, where the usage rate is 2%, or one out of fifty, up nearly 50% from the prior year. According to The State Alcohol and Drug Abuse Profile, well over 300,000 patients entered publicly funded treatment programs primarily for cocaine abuse in 1995, comprising almost 40% of total admissions.
Scientists are continuing to study the neurological effects of this drug, hoping that a better understanding of how the drug affects the brain will result in the development of effective treatments. A drug that would reduce or eliminate the "high" users gain from taking cocaine is a potential weapon in the battle against the ravages of cocaine. One promising area of research is the use of serotonin compounds to modulate the effects of cocaine.
Neurons communicate by sending chemical messengers across small gaps called synapses. An action potential, an electrical signal that originates in the cell body, travels along the axon, resulting in the release of a chemical messenger called a neurotransmitter into the synapse. Neurotransmitters diffuse across the synapse and bind to receptors, proteins found in the membrane of the postsynaptic neuron, which usually results in an action potential in that neuron. Neurotransmitters can be removed from the synapse by proteins called transporters.
One neurotransmitter, dopamine (DA), is associated with processes such as movement and reward. Cocaine affects the system by blocking transporters, which leads to an accumulation of DA in the synapse, thereby increasing the possibility of a postsynaptic response. Mary Ritz found that it is this buildup of DA and subsequent heightened postsynaptic activation which results in the rewarding effects of cocaine. Research has shown that animals such as rhesus monkeys, squirrel monkeys, and rats will readily self-administer dopamine-increasing drugs (agonists), including cocaine. Additional studies, such as one by Marilyn Carroll, have indicated that in addition to DA, serotonin (5-hydroxytryptamine or 5-HT) is also involved in the effects of cocaine. Anatomical, pharmacological and behavioral evidence has indicated an interaction between serotonin and dopamine systems. Since 5-HT acts as a modulator of dopamine activity, 5-HT compounds may be effective medications for cocaine abuse. If 5-HT agonists decrease dopamine activity, a cocaine user is less likely to experience the pleasurable effects of the drug, thereby rendering it less desirable. For example, pretreatment with 5-HT agonists attenuates self-administration of cocaine in animal models.
The study at the Yerkes Primate Center was an examination of the agonists quipazine and alaproclate, two drugs that increase serotonin levels in the brain. It has already been shown in a prior Yerkes study by Paul Czoty that quipazine and alaproclate will decrease responding in squirrel monkeys trained to self-administer cocaine. By utilizing stimulus termination as an alternate method of reinforcement, the specificity of the effects of alaproclate and quipazine on cocaine-maintained behavior have become clearer. It was expected that if the drugs specifically blocked the reinforcing effects of cocaine, the rate of lever pressing would not be significantly lowered. If the drugs were non-specific, the rate should have decreased just as it did in the self-administration study.
In this experiment, six adult male squirrel monkeys (Saimiri sciureus) served as the subjects. Each animal sat in a chamber and was trained to press a response lever in order to receive a reward. In this case, the reward was the termination of a red light that was paired with an impending electrical stimulus. By learning to associate a white light with the reward, the monkeys more closely mimic human cocaine users. The procedure is a good model for cocaine-related behavior in humans, which is often very ritualized. For example, cocaine addicts will often use the drug in the same place with the same people at the same time each week. Users come to associate these particular people and surroundings with the drug, to the point where these peripheral objects can produce a neurochemical effect similar to that of cocaine.
Results of the quipazine experiment indicate that the drug had no significant effect on stimulus termination responding. Although a small decrease in responding was seen after alaproclate administration, it has not yet been determined if this decrease is statistically significant. When compared with the self-administration data, the effect is not nearly as pronounced. These results provide additional support for the theory that quipazine and alaprocate do, in fact, specifically inhibit cocaine’s reinforcing effects. If further studies continue to uphold this theory, it is possible that the long search for a pharmacological cocaine treatment may be drawing nearer to success.
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