Which neurotransmitter deficit is responsible for the motor symptoms in Parkinson disease?

Explanation

## Dopamine Deficiency in Parkinson Disease **Key Point:** Parkinson disease results from loss of dopamine-producing neurons in the substantia nigra pars compacta (SNpc), leading to dopamine depletion in the striatum. This disrupts the balance of direct and indirect motor pathways in the basal ganglia. ### Nigrostriatal Dopamine Pathway ```mermaid flowchart TD A[Substantia nigra pars compacta neurons]:::action --> B[Dopamine synthesis]:::action B --> C[Dopamine release in striatum]:::action C --> D{Basal ganglia motor circuits}:::decision D -->|Normal| E[Coordinated movement]:::outcome D -->|Dopamine loss| F[Bradykinesia, rigidity, tremor]:::urgent ``` ### Basal Ganglia Circuit Imbalance **Normal State:** - Dopamine from SNpc → Striatum - Dopamine activates D1 receptors → facilitates direct pathway (movement) - Dopamine inhibits D2 receptors → suppresses indirect pathway (inhibition of movement) - Net result: balanced motor control **Parkinson Disease (Dopamine Loss):** - Direct pathway is suppressed (↓ D1 activation) - Indirect pathway is disinhibited (↑ D2 activity unopposed) - Net result: excessive inhibition of thalamocortical output → bradykinesia, rigidity **High-Yield:** Dopamine loss must exceed 50–70% before motor symptoms appear. This explains the long preclinical phase and why L-DOPA replacement is effective in early-stage PD. **Mnemonic:** **DRAT** — Dopamine loss Reduces Activity in Thalamus (bradykinesia, rigidity) ### Why Other Neurotransmitters Are Affected But Not Primary | Neurotransmitter | Change | Consequence | |------------------|--------|-------------| | Dopamine | ↓↓ (primary) | Motor symptoms (bradykinesia, rigidity, tremor) | | Acetylcholine | ↑ (relative) | Tremor, rigidity (unopposed cholinergic activity) | | GABA | ↓ | Hyperactivity of indirect pathway | | Glutamate | ↑ | Overactivity of subthalamic nucleus | **Clinical Pearl:** The relative excess of acetylcholine (not absolute increase, but unopposed by dopamine) explains why anticholinergic drugs (benztropine, trihexyphenidyl) provide symptomatic relief, particularly for tremor and rigidity. However, they do not slow disease progression. [cite:Harrison 21e Ch 296]