dopamine Flashcards
cocaine
Cocaine Abuse Decreases Dopamine Receptors, Leading to Anhedonia & Compulsion
Cocaine blocks the dopamine transporter (DAT), preventing dopamine from being reabsorbed and leading to a dopamine buildup in the synapse.
This causes intense euphoria, but with repeated use, the brain adapts by reducing dopamine receptor availability (downregulation).
With fewer receptors, the brain struggles to experience pleasure from natural rewards, a condition called anhedonia (inability to feel pleasure).
Since normal activities no longer produce pleasure, the person compulsively seeks out cocaine to restore dopamine function, reinforcing addiction.
tolerance-
- Excess Dopamine Leads to Receptor Internalization (Tolerance & Increased Dosage Needs)
When a person repeatedly takes an addictive substance, it floods the brain with dopamine, overstimulating the dopamine D1 and D2 receptors in the nucleus accumbens (NAc).
To protect itself from overstimulation, the brain reduces the number of dopamine receptors in a process called receptor internalization (the receptors are pulled into the cell and degraded or recycled).
With fewer receptors available, the same amount of dopamine causes less stimulation, meaning the person needs higher doses of the drug to feel the same effect—this is tolerance.
Over time, natural rewards (e.g., food, relationships) no longer produce pleasure, reinforcing drug-seeking behavior.
Dopamine signalling and
- if there is too much dopamine, the receptor becomes internalised, meaning fewer receptors on outside of neuron and it becomes more difficult to become stimulated- this is tolerance!- this is also called the receptor becomes downregulated
- constantly fighting anhedonia (lack of happiness)
basics-
Key Role: Dopamine is a neurotransmitter that drives reward, motivation, and reinforcement in addiction. Drugs hijack this system, leading to compulsive behavior.
🧠 Ventral Tegmental Area (VTA):
Located in the midbrain, the VTA releases dopamine to key areas, including the nucleus accumbens (NAc) (pleasure center) and prefrontal cortex (decision-making).
Drug use increases dopamine release, reinforcing addictive behavior.
dopamine synthesis and release-
🧪 Dopamine Synthesis:
L-Tyrosine → converted into L-DOPA by tyrosine hydroxylase (rate-limiting step).
L-DOPA → converted into dopamine by DOPA decarboxylase.
🎯 Dopamine Release & Action:
Dopamine is released from neurons in the VTA into the nucleus accumbens (NAc).
It binds to D1 (excitatory) & D2 (inhibitory) receptors, controlling pleasure and reinforcement.
dopamine turnover
🔄 Turnover (Recycling & Breakdown):
Dopamine is reabsorbed via the dopamine transporter (DAT) or broken down by enzymes:
Monoamine oxidase (MAO) → converts dopamine into inactive metabolites.
Catechol-O-methyltransferase (COMT) → further breaks down dopamine.
Drugs like cocaine & methamphetamine block DAT, causing dopamine buildup and stronger effects.
withdrawal-
- Dopamine & Reward System Disruption
During drug use: The Ventral Tegmental Area (VTA) releases dopamine into the nucleus accumbens (NAc), reinforcing pleasure and reward.
After stopping the drug:
Dopamine levels drop sharply due to reduced natural production.
Dopamine receptors (D2) remain downregulated, making it difficult to experience pleasure (anhedonia).
This leads to cravings, depression, and lack of motivation.
dopamine and reward
A reward or a cue with an expected reward leads to increased VTA dopaminergic neuron firing
Lack of expected reward → decreased firing
Corresponding increase/decrease dopamine in nucleus accumbens shell (NAC)
This is important for reward-based learning (operant conditioning) and goal-driven behaviour
Dopamine sensitivity is linked to personality traits like extraversion, sensation- and reward-seeking
Dopamine is targeted by most chemically addictive drugs, but there is also evidence for dopamine independent reward systems
