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dopamine

Dopamine is a key neurotransmitter involved in various brain functions and is associated with several psychiatric disorders, including schizophrenia, depression, and substance abuse. It operates through multiple pathways, affecting emotional behavior, cognitive functions, and motor control. The document also discusses dopamine's synthesis, degradation, receptors, and the impact of various drugs on its activity.

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Indrajeet Rajput
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4 views

dopamine

Dopamine is a key neurotransmitter involved in various brain functions and is associated with several psychiatric disorders, including schizophrenia, depression, and substance abuse. It operates through multiple pathways, affecting emotional behavior, cognitive functions, and motor control. The document also discusses dopamine's synthesis, degradation, receptors, and the impact of various drugs on its activity.

Uploaded by

Indrajeet Rajput
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPTX, PDF, TXT or read online on Scribd
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Dopamine

Dr. Khushboo Kansal


Neurotransmitters
• Are endogenous chemicals that transmit signals
from a neuron to a target cell across a synapse

• Are packaged into synaptic vesicles clustered


beneath the membrane on the presynaptic side of a
synapse, and are released into the synaptic cleft,
where they bind to receptors in the membrane on
the postsynaptic side of the synapse

• Release of neurotransmitters usually follows arrival


of an action potential at the synapse, but may also
follow graded electrical potentials
Types of neurotransmitters
• Major neurotransmitters:
 Amino acids:
 glutamate, aspartate, D-serine, γ-aminobutyric acid

(GABA), glycine

 Monoamines and other biogenic amines:


 dopamine (DA), norepinephrine,
epinephrine ,histamine, serotonin (5-HT)

 Others:
 acetylcholine (ACh), adenosine, anandamide, nitric
oxide, etc.
Dopamine
• Widely distributed through neurons in midbrain,
substantia nigra and ventral tegmental area
and in the periaqueductal gray, hypothalamus,
olfactory bulb, and retina

• Kidney : DA functions to produce renal


vasodilation, diuresis and natriuresis

• Four dopamine systems are highly relevant to


psychiatry : nigrostriatal, mesocortical,
mesolimbic, and tuberohypophyseal system
TYR: Tyrosine, a precursor to dopamine
TOH: Enzyme tyrosine hydroxylase
DA: Dopamine
DDC: Enzyme DOPA Decarboxylase
VMAT2: Vesicular Monoamine Transporter
Degradation
Main enzymes: monoamine oxidase (MAO) and
catechol O-methyltransferase (COMT)
MAO : located on the outer membrane of mitochondria.
 MAO-A
 MAO-B degrades dopamine in and out of neuron

COMT : located in the synapse and is widely distributed


throughout the brain and peripheral tissues
Predominant metabolite : Homovanillic acid (HVA)
Receptors

Adenyl cyclase (AC) : produce cyclic AMP


• Dopamine transporter (DAT) : presynaptic and clears excess dopamine

• Vesicular monoamine transporter (VMAT2) : takes dopamine up into


synaptic vesicles

• Postsynaptic receptors : D-1, D-2, D-3, D-4, and D-5 receptors

• Presynaptic D-2 autoreceptor : regulates release of dopamine


Presynaptic dopamine-2 auto receptors are "gatekeepers" for
dopamine
Pathways
• Projects from the ventral tegmental area to the nucleus
accumbens in the ventral striatum (A) : regulates emotional
behaviours

• Hyperactivity : accounts for delusions and hallucinations (B)


Reward Pathway
Natural high
Substance induced high
Behavioural high
• Projects from ventral tegmental area to the dorsolateral
prefrontal cortex(DLPFC)

• Hypoactivity : negative and cognitive symptoms of schizophrenia


• Projects from ventral tegmental area to ventromedial prefrontal
cortex(VMPFC)

• Hypoactivity : negative and affective symptoms of schizophrenia.


• Projects from substantia
nigra to the basal ganglia
or striatum

• Part of the extrapyramidal


nervous system : key role
in regulating movements

• DA hypoactivity :
parkinsonism with tremor,
rigidity,
akinesia/bradykinesia

• DA hyperactivity :
hyperkinetic movements
like tics and dyskinesia

• Untreated schizophrenia :
normal
• Projects from
hypothalamus to
anterior pituitary :
regulates prolactin
secretion

• Dopamine inhibits
prolactin secretion

• Untreated
schizophrenia : normal
Thalamic Dopamine pathway
 Arises from multiple sites, including the
periaqueductal gray matter, ventral
mesencephalon, various hypothalamic
nuclei, lateral parabrachial nucleus

 Sleep and arousal mechanisms

 No evidence at this point for abnormal


functioning in schizophrenia.
Disorders associated with
dopaminergic system…
Schizophrenia
Mesolimbic pathways : Increase of
Dopamine, positive symptoms

Mesocortical pathways : Decrease of


Dopamine, negative, cognitive and affective
symptoms
Substance Abuse
Nucleus Accumbens : centre for reward
Occurs due to increased release of dopamine
caused by the psychotropic substances :
 Morphine
 Heroin
 Cannabis
 Cocaine
 Nicotine
Depression
Reduction of Dopamine in following areas
 VMPFC- Depressed mood
 PFC, Hypothalamus, Nucleus Accumbens -

apathy
 Nucleus Accumbens Striatum

Hypothalamus - fatigue
 DLPFC - Executive dysfunction
 Nucleus Accumbens ,PFC - Psychomotor

agitation/retardation
Parkinsonism
Parkinsonism : reduced Dopamine in
substantia nigra
Symptoms :
 Rigidity
 Bradykinesia
 Tremors
Others
ADHD :
Reduction in Dopamine Level in anterior
frontal cortex
An area associated with cognitive function
such as
 attention
 concentration

Impulse Control Disorder :


 Reduction in Dopamine Level in
ventromedial prefrontal cortex
Drugs
Dopamine Agonist:
 Levodopa
 Carbidopa
 Ropinirole
Antidepressants:
 Bupropion
Antipsychotics:
 Typical antipsychotic like haloperidol, pimozide
 Atypical antipsychotics like olanzapine, quetiapine,
risperidone
Stimulants:
 Methylphenidate
 Modafinil
Reference

Kaplan & Sadock's Comprehensive Textbo


ok of Psychiatry
Stahl's essential psychopharmacology
THANK YOU

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