Question

What have knockout studies and research with receptor agonists/antagonists contributed to the understanding of the role of dopamine in the mood-elevating effects of psychostimulants? Please provide at least two peer review resources when answering this question (one for knock out studies and other therapeutic drug approaches).

Answer 1

Dopamine is most important hormone in the brain, which is necessary to keep the mood homeostasis. The dopamine can activate 5 G protein-coupled receptors (D1 - D5) in the target cells. With the help of agonist and antagonists, these receptors are targeted and the plethora of information is available today about the action of dopamine and its receptors. Knockout studies which eliminate a gene of interest and receptor studies have led to the deeper understanding of the dopamine as the neurostimulator.
The D1 and D2 are non-selective agonists can reduce the behavioural activation. These receptors are required to reinforce the effects of psychostimulants.
The knockouts of D1 and D2 have shown that D1 receptor is absolutely necessary to reinforce the effects of cocaine. The D2 receptor does not appear to act dominantly in this case. Interestingly the D1 knockouts do not self-administer cocaine ( which causes dopamine-induced pleasure feeling). The D2 knockouts can self-administer with some dose-response differences.
The D3 another receptor acts as antagonists. It blocks the cocaine-related drop in the threshold for electrical synapse. The D3 is an important target for antidepressant actions. The knockout D3 mice have shown to increase resistance to the stressful procedure than the wildtype counterparts.
The role of D4 and D5 dopamine receptors are largely unknown.

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