DOPAMINE NEUROTRANSMITTERS .pptx

Dopamine as neurotransmitter in Brain

1. DOPAMINE NEUROTRANSMITTERS

2. Dopamine Synthesis Dopamine is synthesized by dopaminergic nerve terminals from the amino acid tyrosine. TYR- Tyrosine TOH- Tyrosine hydroxylase DDC- DOPA decarboxylase VMAT2 - Vesicular monoamine transporter

3. Termination of Dopamine’s action DA - Dopamine DAT - Dopamine transporter COMT- Catechol-O-methyltransferase MAO A or B - Monoamine oxidase A or B In cortical dopamine terminal DAT is relatively sparse

4. Dopamine Receptors

5. Dopamine Receptors D2 autoreceptor is less sensitive to dopamine than the D3

6. VTA-ventral tegmental area PFC-prefrontal cortex SN- Substansia Nigra

7. Dopamine Pathways Nigrostrialtal pathway Mesolimbic pathway Mesocortiacl pathway Tuberoinfundibular Pathway

8. The Mesolimbic Dopamine Pathway The mesolimbic Dopamine pathway projects from DA cell bodies in the VTA of the brainstem (i.e., mesencephalon) to the nucleus accumbens in the ventral striatum. Dopamine release from this pathway is thought to have an important role in several normal emotional behaviors, including Motivation Pleasure Reward Too much Dopamine in this pathway classically is thought to cause the positive symptoms of psychosis(delusions and hallucinations) as well as the artificial reward (drug-induced “high”) of substance abuse Hyperactivity of mesolimbic DA neurons may also play a role in causing impulsive, agitated, aggressive, and hostile symptoms in any of the illnesses associated with positive symptoms of psychosis

9. H ypoactivity of the Mesoliombic Pathway is associated with symptoms of anhedonia, apathy, and lack of energy as well as with the negative symptoms of schizophrenia

10. The Mesocortical Dopamine pathway The Mesocortical Dopamine pathway arises from cell bodies of VTA projecting to areas of the prefrontal cortex Branches of the pathway into the dorsolateral prefrontal cortex are hypothesized to regulate cognition and executive functions . Branches of this pathway into the ventromedial parts of prefrontal cortex are hypothesized to regulate emotions and affect

11. The Mesocortical Dopamine pathway Hypoactivity of dopamine neurons in the mesocortical dopamine pathway theoretically mediates the cognitive, negative, and affective symptoms of schizophrenia

12. Tuberoinfundibular Pathway The Dopamine neurons that project from hypothalamus to anterior pituitary Normally, these neurons are tonically active and inhibit prolactin release. In the postpartum state, however, the activity of these Dopamine neurons is decreased. Prolactin levels can therefore rise during breast feeding so that lactation will occur.

13. Tuberoinfundibular Pathway If the functioning of tuberoinfundibular DA neurons is disrupted by lesions or drugs, prolactin levels can also rise. Elevated prolactin levels are associated with galactorrhea ( breastsecretions ), gynecomastia (enlarged breasts especiallyin men), amenorrhea (loss of ovulation and menstrual periods), and possibly other problems such as sexual dysfunction.

14. The Thalamic Pathway This Dopamine pathway that innervates the thalamus arises from multiple sites including the periaqueductal gray matter, the ventral mesencephalon, from various hypothalamic nuclei, and from the lateral parabrachial nucleus . Its function is still under investigation, but may be involved in sleep and arousal mechanisms by gating information passing through the thalamus to the cortexand other brain areas.

15. The Nigrostriatal Dopamine Pathway The Nigrostriatal Dopamine pathway projects from Dopamine cell bodies in the brainstem substantia nigra via axons terminating in the striatum. It is a part of the extrapyramidal nervous system, It is involved in the control motor movements via its connections with the thalamus and cortex in cortico- striato - thalamo -cortical (CSTC) circuits or loops.

16. GABA- Glutamate- A γ-aminobutyric acid (GABA) neuron projecting from the striatum to the globus pallidus interna is activated. The released GABA inhibits activity of another GABAergic neuron that projects to the thalamus. In the absence of GABA release in the thalamus, a glutamatergic neuron is activated and releases glutamate into the cortex, stimulating movement

17. A γ-aminobutyric acid (GABA) neuron projecting from the striatum to the globus pallidus externa is activated. The released GABA inhibits activity of another GABAergic neuron that projects to the subthalamic nucleus (STN). In the absence of GABA release in the STN, a glutamatergic neuron is activated and releases glutamate into the globus pallidus interna, which in turn stimulates a GABAergic neuron to release GABA into the thalamus. GABA then binds to a glutamatergic neuron, inhibiting it from releasing glutamate into the cortex and thus inhibiting movement.

18. New Developments in the Dopamine Hypothesis of Positive Symptoms of Psychosis in Schizophrenia

19. A classic understanding of striatal functioning has been that the dorsal striatum regulates motor movement and the ventral striatum regulates emotions, with overactivity of dopamine in the ventral striatum associated with the positive symptoms of schizophrenia. Neuroimaging data in unmedicated patients with schizophrenia suggest that dopaminergic activity may be unaltered in the ventral striatum, but may instead be overactive in an intermediate part of the striatum called the associative striatum, which receives input from the substantia nigra rather than the ventral tegmental area (VTA).Rather than separate nigrostriatal and mesolimbic projections, a better conception may be that of a mesostriatal pathway .

20. To Sum up (a) The nigrostriatal dopamine pathway, controls motor function and movement. (b) The mesolimbic dopamine pathway a involved in many behaviors such as pleasurable sensations, the powerful euphoria of drugs of abuse,and delusions and hallucinations of psychosis. (c) The mesocortical dopamine pathway have a role in mediating cognitive symptoms (dorsolateral prefrontal cortexor DLPFC) and affective symptoms (ventromedial prefrontal cortex or VMPFC) of schizophrenia. (d) The tuberoinfundibular dopamine pathway controls prolactin secretion. (e) The Thalamic dopamine Pathway function is not well known

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