Mechanism+of+Action+for+Antipsychotics

__ **Dopamine Theory of Schizophrenia** __ Essentially, The Dopamine Theory of Schizophrenia asserts that both the positive and negative symptoms of schizophrenia are associated with a dyregulation of the neurotransmitter Dopamine (DA). Chiefly, in the central nervous system, more specifically the brainstem, DA causes a dysregulation of the dopaminergic brain pathways that in turn causes both an overactivity of dopaminergic neurons which produces the positive symptoms of schizophrenia and an under-activity of prefrontal dopaminergic neurons which produces the negative symptoms of schizophrenia (Bishara & Taylor, 2008). Dopaminergic functions are regulated by four major DA subsystems, the Nigrostriatal System, the Tuberoinfundibular System, the Mesolimbic System and the Mesocortical System, all of which are effected by the overactivity or under-activity of DA (Bishara & Taylor, 2008). Generally speaking, excess or lack DA has different effects on each of the four systems some of which contribute to both the negative and positive effects of schizophrenia.

**Dopaminergic System** [|Dopamine Pathway Video]

(Untitled photograph of brain, n.d.)

Fundamentally, research studies have provided evidence for the Dopamine Theory of Schizophrenia by demonstrating that typical antipsychotic drugs, which are dopamine receptor antagonists, reduce schizophrenia symptoms. Simply put, there are two types of dopamine receptors D1 receptors which has two subtypes, D1 and D5 and D2 receptors which has three subtypes, D2, D3, D4 and antipsychotics have an affinity for the D2 receptors and work by blocking DA from entering the receptor sites which inhibits DA activity (Brudzynski, 2010). Nonetheless, these antipsychotics are not selective in the DA subsystem receptors that they inhibit. Thus, antipsychotics effect each of the four major DA subsystems even if there are not responsible for either positive or negative schizophrenic symptoms (Brudzynski, 2010).

(Untitled photograph of action of antipsychotic, 2010) Firstly, the Nigrostriatal System is important for motor control and when DA is blocked in this subsystem by antipsychotics there are several side effects such as extrapyramidal disorders, tardive dyskinesia and Parkinson’s like symptoms, such as difficulty in starting and stopping movements, demonstrating an abnormal posture and tremors (Brudzynski, 2010).

Secondly, the Tuberoinfundibular System is responsible for neuroendocrine control and antipsychotic medications produce the increased release of prolactin which can cause lactation (in both women and men), headaches, sexual dysfunctions and visual problems(Brudzynski, 2010).

Thirdly, the Mesolimbic System is associated with positive emotions, pleasure and motivation as DA travels from the brain stem to the limbic system and into the nucleus accumbens. Antipsychotic medications target the Mesolimbic system to combat the overactivity of DA which causes the positive symptoms of Schizophrenia, delusions and hallucinations in particular. Thus, the blocking of DA receptors in the Mesolimbic system reduces positive symptoms and behavioural disturbances but can also lead to a loss of motivation and happiness(Brudzynski, 2010).

Lastly, the Mesocortical System is responsible for cognition such as thinking, reasoning, memory and planning and has a lack of DA in the Mesocortical system is responsible for the negative symptoms of Schizophrenia. Therefore, blocking DA receptors in this system reduces the already deficit of DA and thus has mixed effects and can even cause secondary negative symptoms(Gray & Roth, 2007).

Overall, although antipsychotics drugs have been proven to reduce the positive symptoms of Schizophrenia there is still controversy as to if they reduce the negative symptoms of Schizophrenia (Gray & Roth, 2007). Thus, in order for new medications to be effective in relieving both the positive and negative symptoms there needs to be a complete understanding of the mechanisms of Schizophrenia.

**The Mechanism of Antipsychotic Medication** media type="youtube" key="nGqo7ZQc6Sg" height="315" width="420" align="center" (Clerainc, 2010)

__ **The Role of Serotonin** __ In addition to the effects on the dopaminergic system, antipsychotic medications also have effects on the neurotransmitter Serotonin (5-HT). More specifically, atypical antipsychotic medications are focusing on 5-HT receptors and their ability to modulate the dopaminergic tone, especially in the Mesocortical system which is thought to be source of the negative symptoms of schizophrenia. Simply put, 5-HT's role in the treatment of schizophrenia is to increase the DA levels in the prefrontal cortex in order to reduce the negative symptoms (Gray & Roth, 2007).