Dopamine reward systems

Given the low incidence of severe withdrawal symptoms and the modest effects on the mesolimbic dopamine (reward) system, most investigators have found that cannabis has a low abuse or addiction potential. However, it has been argued that if cannabis is a non-addictive substance, why is its use so widespread and why are there so many longterm and heavy users Finally, contrary to the evidence that cannabis can produce chronic tolerance, some regular users report that they require less drug to achieve the same high, or sensitisation (Chapter 3). Three possible explanations may account for this. First, chronic users may focus on the effects that they wish to achieve. Second, the... 

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

QUESTION If the reward system is not being activated, for whatever reason, is dopamine considered to be more of a neurotransmitter of the reward system ... 

FIGURE 33-3. Location of the dopamine neural tracts associated with the reward system in the brain. Data from reference 5. (From http //www.drugabuse.gov/pubs/Teaching/) ... 

The behavioral effects of nicotine have been defined as both stimulant and depressant, effects that are influenced by the present mental status and expectations of the smoker. Smokers may feel alert and relaxed. Nicotine produces myriad effects on the central nervous system (CNS), almost all of which appear to be mediated through nicotinic receptors. Additionally, nicotine influences multiple neuronal systems. One of its most prominent effects is stimulated release of dopamine, particularly in the nucleus accumbens, which is a major component of the reward system. Nicotine also stimulates the release of endogenous opioids and glucocorticoids. 

Dopamine also appears to be important in affiliative behaviors. Dopamine is well known for its role in the reward systems of the brain, and this role most likely extends to social behaviors as well. In prairie voles, the Dj receptors appear to play an important role in partner preference formation after mating (Insel and Young, 2001). The specific role has yet to be elucidated, however, agonists can facilitate this behavior and antagonists of the D2 receptor can inhibit it. 

All three major brain dopamine (DA) systems (nigros-triatal, mesocortical, and mesolimbic) have been implicated in aggression in animal studies (Miczek et ah, 1994). Brain DA systems appear to be involved in (1) the rewarding or reinforcing aspects of aggression, possibly via mesolimbic and mesocortical DA systems and (2) the initiation, execution, and termination of aggressive behavior patterns, possibly via the nigrostriatal and mesolimbic DA systems. 

Researchers begin to examine dopamine s role in the brain s reward system and in the reinforcing aspects of drugs of abuse. 

In this area, too, neurobiological research has brought increasing knowledge. Cocaine and amphetamines act directly on synapses in the reward system to increase the amount of transmitter dopamine present. Several catecholamine transmitters are additionally involved in brain areas outside the reward system. This might explain the immediate effects, the euphoria produced, and the profile of the experiences. 

These smoked substances interact with the brain s own cannabinoid receptors to trigger dopamine release from the mesolimbic reward system. There are two known cannabinoid receptors, CB1 (in the brain, which is coupled via G proteins and modulates adenylate cyclase and ion channels) and CB2 (in the immune system). The CB1 receptors may mediate not only marijuana s reinforcing properties, but also those of alcohol. There is also an endogenous cannabinoid system (the brain s own marijuana) capable of activating these cannabinoid receptors functionally. These ert-docannabinoids are synthesized by neurons and inactivated by reuptake systems and enzymes in both neurons and glia. 

Nicotine is thought to cause addiction primarily through its action to increase the levels of dopamine, which activates the brain circuitry that regulates feelings of pleasure and motivation, the so-called reward system. Increased dopamine in this system produces pleasurable sensations, as seen in other drugs of abuse such as cocaine and heroin. 

Neurotransmission events involved in the sensation of reward are also important. Alcohol affects local concentrations of serotonin, opioids, and dopamine—neurotransmitters involved in brain reward circuits. Alcohol also has complex effects on the expression of receptors for these neurotransmitters and their signaling pathways. The discovery that naltrexone, a nonselective opioid receptor antagonist, helps patients who are recovering from alcoholism abstain from drinking supports the idea that the neurochemical reward system is shared by drugs associated with physical and psychological dependence. 

Dopamine is also an important component of the brain s reward system and is believed to play a role in drug addiction. Increased levels of dopamine have been associated with cocaine, amphetamine, and marijuana use, as well as alcohol and nicotine addiction, see also Neurotransmitters. 

One of nicotine s effects is to increase the concentration of dopamine, a chemical in the brain s reward system. Release of this chemical makes smokers feel good and reinforces the need to smoke. 

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