Mesolimbic Pathway

The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area, which is located in the midbrain, to the nucleus accumbens and olfactory tubercle, which are located in the ventral striatum.

The release of dopamine from the mesolimbic pathway into the nucleus accumbens regulates incentive salience (i.e., motivation and desire) for rewarding stimuli and facilitates reinforcement and reward-related motor function learning; it may also play a role in the subjective perception of pleasure. The dysregulation of the mesolimbic pathway and its output neurons in the nucleus accumbens plays a significant role in the development and maintenance of an addiction.

There is some controversy regarding dopamine’s role. Three hypotheses — hedonia, learning, and incentive salience — have been proposed as explanations for dopamine’s function in the reward system. The hedonia hypothesis suggests that dopamine in the nucleus accumbens acts as a ‘pleasure neurotransmitter.’ Historically, in the late 1970s, it was found that some drugs of abuse involved dopamine activity, particularly in the nucleus accumbens, to cause the ‘high’ or euphoric state. However, not all rewards or pleasurable things involve activation of the reward system, which may suggest that the mesolimbic pathway may not be just a system that works merely off enjoyable things (hedonia).

Learning, on the other hand, deals with predictions of future rewards and association formation. Studies have shown that rats that had their ventral tegmental area and nucleus accumbens destroyed do not lose their learning capabilities, but rather lack the motivation to work for a reward. Incentive salience (wanting) stands out as a possible role for dopamine as it regards this molecule as being released when there is a stimulus worth working hard for, thus making an individual work to get it. This is one of the reasons why dopamine transport has been extensively studied in the case of ADD and ADHD.

It is now widely understood that most people suffering from some form of attention deficit disorder most likely lack dopamine stimulation. This also explains why dopamine reuptake inhibitors and stimulants often dramatically improve symptoms of attention disorders. In self-administration studies, animals have been trained to give an operant response (lever press, nose poke, wheel turn, etc.) in order to obtain either a drug or mate. It has been shown that the animals will continue to perform the required task until the reward is received, or fatigue sets in.

Since the mesolimbic pathway is shown to be associated with feelings of reward and desire, this pathway is heavily implicated in neurobiological theories of addiction, schizophrenia, and depression. Drug addiction, the loss of control over drug use or the compulsive seeking and taking of drugs despite adverse consequences, with the four major classes of abused drugs (psychostimulants, opiates, ethanol, and nicotine) are due to increased dopamine transmission in the limbic system-each by different mechanisms. Like drug addiction, schizophrenia and depression have similar structural changes with dopamine transmission.

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