Cocaine in your brain
Cocaine is a psychoactive drug affecting the central nervous system. It is prepared from the leaf of the Erythroxylon coca bush, which grows primarily in Peru and Bolivia. This drug is self administered in several ways. The most common method of cocaine abuse is snorting it (in powder form) into the nasal sinuses, either alone or with heroin (speedball). It is generally sold on the street as a hydrochloride salt - a fine, white crystalline powder known as coke, C, snow, flake, or blow. Another method of administration, which produces its effects more quickly, is smoking it in the form of crack cocaine.
Cocaine produces a wide range of physiological effects in humans, including the stimulation of a plethora of emotional experiences. When people take cocaine, they become euphoric, highly active (locomotion, tremors, and tics), and more talkative than normal. They experience feelings of extreme power and alertness. This initial high is followed by bouts of severe anxiety, paranoia, and depression, which often lead to addiction. Those who become addicted to the drug often turn the habit into an obsession, so that they devote more, and more of their time and money to acquiring and using the drug.
People who abuse these drugs regularly often exhibit psychotic behavior such as hallucinations, delusions of persecution, mood disturbances, and repetitive behaviors, all of which closely resemble the symptoms of paranoid schizophrenia. Trained mental health professionals have trouble telling a schizophrenic and a cocaine addict apart unless they know the patient's background. Although the psychological and behavioral effects of cocaine use in humans have been well documented, the current knowledge of the neurological basis for the abuse of cocaine in humans is still limited. The majority of knowledge we possess about the mechanisms of the effects of cocaine comes from animal studies performed over the last 20 years. These studies have clearly demonstrated the crucial role of the neurotransmitter dopamine in initiating many of the effects of cocaine use.
Cocaine has an extremely rapid euphorogenic effect on the user, especially in the case of the smoking method of use, because the drug directly enters the pulmonary blood stream when smoked. Cocaine has a relatively short half-life in the plasma and in the brain. When administered intravenously (IV) to humans, the half-life is in the range of 16 to 87 minutes (18 to 30 minutes in rats). This short half-life accounts for the rapid euphorogenic effects of the drug. Typically, when the drug is administered intravenously, it produces a fast "hit-and-run" effect on the potentiation of the extracellular levels of dopamine. When rats are given a continuous flow of dopamine intravenously, they experience a peak in dopamine levels in 10 minutes, followed by a return to regular levels after 20 to 30 minutes (Hurd and Ungerstedt 1989). Because the initial high experienced by cocaine abusers lasts for only a short time, the initial stimulatory actions of cocaine can be attributed to the elevation of synaptic dopamine levels.
When the dopamine levels return to normal, a diversity of psychological and behavioral effects of the cocaine use still exist, especially those associated with unpleasant emotions. Fifteen minutes after an IV injection of cocaine, the subject experiences a craving for more cocaine, even though a high concentration of cocaine should still be present in the brain (Jaffe et al. 1989). It has also been shown that after the self-reported rush of the cocaine high has diminished, continuous IV infusion of cocaine will often induce negative feelings such as dysphoria, anxiety, and paranoia, which are mixed with positive feelings of well being (Kumor et al. 1989). This tells us that even with a steady flow of cocaine to the brain, a cocaine user will still be subject to the negative effects of the drug use, because his dopamine levels will drop back to normal even though the brain is saturated with cocaine. So, the constant abuse of, and addiction to cocaine are characterized by a state in which the negative dysphoric effects are experienced regularly due to the brains compensatory mechanisms for maintaining normal dopamine levels. Since subjects still experience negative effects with normal dopamine levels (Kumor et al. 1989), this leads to the theory that cocaine must also exert its effects (especially the aversive effects) through mechanisms other than the dopamine system. The involvement of opioid neuropeptides in causing the negative effects of cocaine abuse is likely.
The nucleus accumbens is a critical site for the reinforcing effects of cocaine. It is located in the basal forebrain, rostral to the preoptic area, and immediately adjacent to the septum. It is part of the neostriatum (ventral striatum), which integrates information related to motor coordination, emotion, and motivation. The nucleus accumbens receives dopamine-secreting terminal buttons from neurons of the ventral tegmental area, and it is thought to be involved in reinforcement and attention. Studies done with microdialysis have shown that natural reinforcers trigger the release of dopamine in the nucleus accumbens. Behaviors such as drinking water when dehydrated, eating salty foods in response to sodium depletion, etc, are reinforced by increasing the dopamine concentration in the nucleus accumbens (Blander et al 1988). Other research has shown that the nucleus accumbens is a critical site for the reinforcing effects of cocaine abuse. Rats will learn to press a lever that causes the injection of a small quantity of amphetamine into the nucleus accumbens (Hoebel et al. 1983). Amphetamine is used instead of cocaine because the injection of cocaine has an anesthetic effect, which would counteract the stimulatory effects. When dopamine receptor blockers are injected into the nucleus accumbens, cocaine no longer has a reinforcing effect (McGregor and Roberts, 1993). This provides further evidence for the reinforcing function of the nucleus accumbens.
Opioid peptides play a physiological role in a wide variety of behaviors, including mood, motivation, and extrapyramidal motor function (Herz 1993). Cocaine abusers often combine heroin (an opiate) and cocaine to make a speedball, which helps them to avoid some of the negative dysphoric and anxious feelings induced by cocaine alone (Kreek 1988). Animal studies have shown a strong involvement of the opioid system in the reinforcing actions of cocaine. A study by Bain and Kornestsky et al. 1987 demonstrated that the opiate antagonist naloxone reduces the rewarding effects of cocaine on self-stimulation behavior. This is reinforced by the fact that, although withdrawal from long-term cocaine abuse does not lead to negative physical symptoms, it does cause unpleasant feelings, including dysphoria and decreased ability to experience pleasure.
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