PARKINSONS ANMD DOPAMINE

Parkinson's Disease

A progressive neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra.

Dopamine

A neurotransmitter involved in movement, reward, and behaviour.

Basal Ganglia

A group of brain nuclei that control and coordinate movement.

Components of Basal Ganglia

Striatum, Globus pallidus, Substantia nigra, Subthalamic nucleus.

Motor Cortex

Initiates and controls movement.

Function of Basal Ganglia

Prevents unwanted movement and refines intended movement.

Glutamate

An excitatory neurotransmitter (accelerator).

GABA

An inhibitory neurotransmitter (brakes).

Dopamine's Role in Basal Ganglia

Modulates movement pathways.

Motor Symptoms of Parkinson's

Tremor, Rigidity, Bradykinesia.

Bradykinesia

Slowness of movement.

Gait Changes in Parkinson's

Shuffling, hunched posture, reduced fluidity.

Neurons Affected in Parkinson's

Dopaminergic neurons in substantia nigra.

Lewy Bodies

Protein aggregates inside neurons (α-synuclein).

Harmful Effects of Lewy Bodies

Produce ROS leading to neuronal death.

ROS (Reactive Oxygen Species)

Neurotoxic molecules that can lead to cell damage.

Early Non-Motor Symptoms

Constipation, Mood disorders, Sleep problems.

Late Parkinson's Complications

Dementia, Psychosis, Postural instability.

Main Functions of Dopamine

Movement, Reward, Decision making, Motivation.

Main Reward Pathway

VTA → nucleus accumbens → prefrontal cortex.

VTA (Ventral Tegmental Area)

Origin of dopamine in the reward system.

Dopamine Release

Occurs from the presynaptic neuron.

Dopamine Removal

Dopamine transporter (DAT) removes dopamine from the synapse.

Dopamine Packaging

VMAT (vesicular monoamine transporter) packages dopamine.

Too Much Dopamine Stimulation

Leads to receptor internalisation (downregulation).

Importance of Dopamine Regulation

Reduces reward and leads to tolerance.

Classical Conditioning

Association between a neutral stimulus and a meaningful stimulus.

Operant Conditioning

Behaviour shaped by reward or punishment.

Definition of Reward

Behaviour leading to a positive outcome.

Behaviour Strengthened by Dopamine Release

Dopamine release strengthens behaviours associated with rewards.

Key Features of Addiction

Compulsive use, loss of control, continued use despite harm.

Cause of Tolerance

Reduced receptor sensitivity due to repeated stimulation.

Effects of Stimulants like Methamphetamine

Increase dopamine release and damage dopamine neurons.

Long-Term Effects of Methamphetamine

Reduced DAT and Parkinson-like symptoms.

How Stimulants Cause Damage

Microglia become activated, producing ROS which leads to neuron death.

First-Line Treatment for Parkinson's

L-DOPA.

Reason Dopamine Cannot Be Given Directly

Dopamine cannot cross the blood-brain barrier.

Side Effects of L-DOPA

Nausea, Psychosis, Insomnia, Tremors.

Examples of Dopamine Agonists

Pramipexole, Ropinirole.

Risk of Dopamine Agonists

Potential for compulsive behaviours.

Deep Brain Stimulation

Electrical stimulation of brain areas to improve movement.

Cannabinoids

Compounds that act on CB receptors.

Main Cannabinoid Receptors

CB1 (brain) and CB2 (immune system).

Cannabinoid Mechanism of Action

Inhibit calcium channels, open potassium channels, reduce neurotransmitter release.

Positive Effects of Cannabinoids

Pain relief, reduced rigidity, anti-anxiety effects.

Negative Effects of Cannabinoids

Memory loss, hallucinations, paranoia.

Nicotine Action on Receptors

Acts on nAChRs (nicotinic acetylcholine receptors).

Type of Nicotinic Receptor

A ligand-gated ion channel.

Effect of Nicotine on Dopamine

Increases dopamine release.

Why Nicotine is Addictive

It strongly activates the reward pathway.

Dopamine Loss and Parkinson's Symptoms

Loss of dopamine leads to imbalance in basal ganglia, causing excessive inhibition of movement and bradykinesia.

Role of α-synuclein in Parkinson's

Misfolding and aggregation lead to Lewy bodies, which produce ROS and cause neuronal death.

Mechanism of Addiction Development

Repeated dopamine release causes receptor downregulation, leading to tolerance and compulsive behavior.

Link between Stimulants and Parkinson's Disease

Stimulants damage dopaminergic neurons and reduce DAT, increasing neurotoxicity and leading to Parkinsonism.