one of the negative symptoms of schizophrenia, known as flat affect, involves:

Antipsychotics can block D2 receptors in this pathway reducing pleasure effects. The mesolimbic pathway is also the site of the rewards pathway and mediates pleasure and reward.Hyperactivity of dopamine in the mesolimbic pathway mediates positive psychotic symptoms.The pathway projects from the ventral tegmental area (VTA) to the nucleus accumbens in the limbic system.Dopaminergic transmission in the prefrontal cortex is mainly mediated by D1 receptors, and D1 dysfunction has been linked to cognitive impairment and negative symptoms of schizophrenia.Furthermore, dopamine synthesis capacity has also been shown to steadily increase with the onset of severe psychotic symptoms. There is compelling evidence that presynaptic dopamine dysfunction results in increased availability and release of dopamine and this has been shown to be associated with prodromal symptoms of schizophrenia.

Valbenazine a highly selective VMAT2 inhibitor has been approved by the FDA for the treatment of tardive dyskinesia.Methamphetamine increases extracellular dopamine by interacting at vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine uptake and promote dopamine release from synaptic vesicles, increasing cytosolic dopamine available for reverse transport by the dopamine transporter (DAT).Carbidopa prevents the conversion of levodopa to dopamine in the periphery, thus allowing more levodopa to pass the blood-brain barrier to be converted into dopamine for its therapeutic effect. Carbidopa is a peripheral DOPA-decarboxylase inhibitor co-administered with levodopa.

Its expression is significantly increased in the substantia nigra of schizophrenia patients when compared to normal healthy subjects. Tyrosine hydroxylase is the rate-limiting step in the production of dopamine.When dopamine is released during neurotransmission, it acts on 5 types of postsynaptic receptors (D1-D5).Ī negative feedback mechanism exists through the presynaptic D2 receptor which regulates the release of dopamine from the presynaptic neuron.Īny excess dopamine is also ‘mopped up’ from the synapse by Dopamine transporter (DAT) and stored in the vesicles via VMAT2.ĭopamine is broken down by monoamine oxidase A (MAO-A), MAO-B and catechol-o-methyltransferase (COMT).

This dopamine is packed and stored into synaptic vesicles via the vesicular monoamine transporter (VMAT2) and stored until its release into the synapse. Tyrosine is converted into DOPA by the enzyme tyrosine hydroxylase.ĭOPA is converted into dopamine (DA) by the enzyme DOPA decarboxylase (DOPADC). Dopamine is synthesised from the amino acid tyrosine.

One of the negative symptoms of schizophrenia, known as flat affect, involves: