Mechanism

The mechanism of behavior is a system or process that produces a regular phenomenon. In this case, we are focusing on the biological mechanism of the mesotelencephalic dopamine system, or the reward system, and its relattion to motivation and drug addiction.

For a basic explanation of neurons and how they work in relation to reward please visit: http://learn.genetics.utah.edu/content/addiction/reward/

(Left: a rat lever pressing for a dopamine increasing drug or stimulation of the reward circuit. Right: A rhesus monkey lever pressing for a juice reward with an invivo microdialysis machine attached to its head)

The mesotelencephalic dopamine pathway has been determined as playing a significant role in addiction across animal species. This pathway is composed of dopaminergic neurons that project from the midbrain to the telencephalon. In laymanís terms, this means that neurons that can both release and accept dopamine, a neurotransmitter that has been shown to play a large role in reward and motivation, connect the midbrain which handles many basic actions of the brain (sleep, vision, hearing, motor control, temperature regulation, etc.) to part of the forebrain which controls more complicated functions (learning and memory, communication, sensory processing, etc.).

dopamine pathways, brain

(The green arrows in the diagram above demostrates the multiple pathways of dopamine in the brain)

This system has been studied repeatedly to ascertain whether it plays a role in addiction and there are four major reasons that lend to it being important:

1. Mapping studies: Areas that are implicated in self-stimulation (such as self-administering cocaine, or even lever pressing for an intracranial electric stimulation at a specific point) are within this reward system.

2. In vivo cerebral microdialysis: When a live animal has a small semi-permeable membrane inserted into a specific part of the brain that can constantly collect fluid that can be assessed for neurotransmitter content. It has been shown that dopamine in the synapse increase with cocaine self-administration, and with self-stimulation.

3. Agonist/antagonist studies: It has been shown that dopamine agonists (something that increases the effectiveness of dopamine) increase self stimulation and antagonists (something that blocks the effect of dopamine) decreases self-stimulation

4. Lesion studies: When parts of the mesotelencephalic dopamine system are lesioned (either by chemically killing the cells or physically cauterized or otherwise damaging the cells at a specific area) self-stimulation is decreased. Specifically, if one lobe is damaged and the other remains intact as a control, self stimulation is decreased to the damaged side but not the other.

Cocaine's effects on dopamine

(How cocaine affects dopamine on an individual pre-synaptive neuron, synapse, and post-synaptic neuron)

Cocaine specifically is an example of a drug called a stimulant. It works by blocking the reuptake of dopamine after it has been released into the synapse. Part of the reason why cocaine is addictive is because as cocaine blocks the reuptake of dopamine, more of it floods the synapse and as such there is more available for uptake by dopamine receptors on the postsynaptic membrane. The problem is that neurons are self-regulating. If the neuron can receive an equal amount of dopamine that it needs but with less receptors, those receptors will go away. Then, after the drug has been metabolized out of the system, there will not be enough dopamine transferred because reuptake has started up again, so there is less dopamine in the synapse and fewer receptors for it to bind to and thus feelings of reward and motivation are gone. The feeling that a person does not just want, but NEEDS the drug, stems from this mechanical problem.

(An audoradiogram of a rhesus monkey on cocaine, and which receptors are bound to)

Rhesus monkeys are often used to identify if an agonist/antagonist,(something that stimulates firing by adhering to a receptor or decreases firing respectively), of a specific neurotransmitter receptor can decrease the self-administration of a drug of abuse after injection of the agonist.