The Role Of Dopamine As An Antidepressant Medication
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The neural circuitry that controls mood under normal and abnormal conditions remains incompletely understood. Depression is the most common of the affective disorders and is linked worldwide to disability and premature death (Rang H.P., Dale M.M., Ritter J.M., & Moore P.K, 2003). Over the past four decades, inhibitors of biogenic amine reuptake have been the main drug therapy for the treatment of major depression, specifically 5-hydroxytryptamine (serotonin) reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants. The purpose of this essay is to hypothesis as to why there are not more antidepressant drugs that directly affect dopamine in the brain. A possible reason is the findings that though dopamine is shown to have a role in the mesolimbic pathway, the role of dopamine in neurotransmission and the effect of manipulation of levels through antidepressants are still largely unknown. The limited focus on dopamine could also have been a result of the extensive evidence that the more commonly used antidepressants (such as SSRIs, SNRIs, and tricyclics ) work very well, as well as the lack of success achieved with use of available dopamine-enhancing medications. Finally, post-mortem studies of the dopaminergic neurotransmission system in depressed patients show inconclusive findings which do not support the hypothesis that depression will be decreased by a direct effecting on dopamine levels in the brain (Dunlop B.W. & Nemeroff C.B., 2007).

Dopamine is involved in a variety of brain functions and pathways, and produces both excitatory and inhibitory postsynaptic potentials. Dopamine is synthesized in the presynaptic neuron from the amino acids phenylalanine and tyrosine. “Phasic” dopamine release is characterized by burst firing and is thought to occur in response to behavioral stimuli, such as those that may predict reward. In contrast, “tonic” dopamine release is slow and irregular. Dopamine is released from the axon extension of the presynaptic neuron for binding on the postsynaptic neuron at two classes of receptors: the dopamine 1 (D1) family, comprising D1 and D5 receptors, and the D2 family that includes D2, D3, and D4. Dopaminergic synapses include the mesolimbic pathway, the nigrostriatal pathway, and the mesocortical pathway. The mesolimbic system plays an important role in reinforcing effects of certain categories of stimuli and is thought to be involved in producing pleasurable feelings. Dopamine’s role in the nigrostriatal pathway is an important component of the basal ganglia modulation of movement (deficiency in this pathway will lead to the motor condition of Parkinsons disease). Neurons in the mesocortical system have an excitatory effect on the frontal cortex and are believed to be involved in functions such as the formation of short-term memories, planning, and strategy preparation for problem solving (Carlson, 2004). Thus the involvement of dopamine in multiple brain functions may explain the dilemma associated with the use of dopamine-related drug therapies. For example, if dopamine levels are boosted in an attempt to enhance its effects in the mesolimbic pathway and so reduce anhedonia, it is possible that other systems impacting movement, the creation of short-term memories, planning and strategy preparation for problem solving etc will also be impacted. This may lead to significant unwanted consequences in the patient, quite separate to any effect on anhedonia.

Since the identification of the first effective antidepressant, iproniazid, the neurotransmitters serotonin, norepinephrine, and dopamine have been proposed to have antidepressant effects (Goodale E.P. & Tucker V.L., 2005). Scientific and clinical research conducted over the following decades following confirmed that serotonin, norepinephrine and dopamine all play a critical role in the etiology of depression. Investigation into the effects of antidepressants, however, did not highlight the importance of dopamine but rather showed considerable evidence to support the role of the serotonin system in exerting the antidepressant response in humans. The efficacy of tricyclic antidepressants (such as iproniazid) was largely due to their ability to inhibit the reuptake of norepinephrine and serotonin (Dunlop B.W. & Nemeroff C.B., 2007).

Different types of antidepressant treatments were shown to enhance serotonin neurotransmission via different pre- or postsynaptic mechanisms which led to the development of the selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs). Though both these antidepressants affect dopaminergic neurotransmission they do not directly enhance dopamine transmission. The available antidepressants that directly enhance dopaminergic neurotransmission often have negative or inconsistent results in depressed patients. Nomifensine, a potent dopamine and norepinephrine reuptake inhibitor was withdrawn from medical use due to its potential for abuse and other concerns. Amineptine, which blocks dopamine reuptake, is no longer available in most countries. Wellbutrin blocks dopamine reuptake, but only binds to 22-26 percent of the dopamine transporter sites while SSRIs block 80 percent or more of serotonin transporter sites. Medications used to treat Parkinson’s, which act as D2 agonists, have shown some promise for treating depression but only in small studies with inconsistent results (Rang H.P., Dale M.M., Ritter J.M., & Moore P.K, 2003).

The few available postmortem studies of the dopamine system in depressed patients have provided conflicting results. For example brain concentrations of dopamine

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Role Of Dopamine And Tricyclic Antidepressants. (July 21, 2021). Retrieved from https://www.freeessays.education/role-of-dopamine-and-tricyclic-antidepressants-essay/