Dopaminergic Pathways

What are dopaminergic projections?

Dopaminergic projections are places with the most dopaminergic neurons?

Dopamine is important for what pathways?

Mesostriatal, ventral tegmental area, arcuate nucleus

What is the mesostriatal pathway involved with?

The mesostriatal pathway is involved with motor functions

What is the ventral tegmental area involved with?

Reward and addiction

What is the arcuate nucleus involved with?

Reward and addiction

How many dopamine receptors do we have? What kind of receptors are they?

D1 - D5; Metabotropic

What dopamine receptors are coupled to Gs?

D1 and D5

What dopamine receptosr are coupled to Gi/o?

D2 - D4

Where can D1 receptors be found?

CONN; Cerebral Cortex; Olfactory Tubercle; Neostriatum; Nucleus Accumbens

Where can D2 receptors be found?

NON; Nucleus accumbens; olfactory tubercle; and neostriatum

Where can D3 receptors be found?

Nucleus accumbens and islands of Calleja

Where can D4 receptors be found?

Midbrain and the amygdala

Where can D5 receptors be found?

The hippocampus and the hypothalamus

What is the precursor of dpaminergic neurons?

Tyrosine

What enzyme breaks down tyrosine?

Tyrosin hydroxylase

What can inhibit tyrosine hydroxylase?

AMPT, which stops dopamine synthesis

What packages dopamine into vesicles?

VMAT

What can inhibit VMAT?

Resperine, which depletes dopamine storage

What is the transporter for dopamine called?

Dopamine transport (DAT)

What can inhibit dopamine transporter?

Cocaine

What can increase the release of dopamine from dopamine transporter?

Amphetamine

What receptors function as autoreceptors in the dopaminergic system?

D2 and D3

What proteins are coupled to Gs in the postsynaptic membrane?

D1 and D5

What is MAO and COMT?

MAO and COMT are enzymes that break down dopamine into HVA

What can inhibit MAO?

Selegiline (specifically MAOB)

What can inhibit COMT?

Tropolone

What are some examples of things that can act as positive reinforcement?

Food, sex, and drugs

What drugs can influence the mesolimbic (reward) circuit

Alcohol, nicotine, stimulants, opioids, cannabinoids

What are the five types of tolerance?

Pharmcodynamic, pharmcokinetic, behavioral, cross, and reverse tolerance

What is pharmcodynamic tolerance?

Pharmcodynamic tolernace is the change of receptor number or sensitivity

What is pharmacokinetic tolerance?

Pharmcokinetic tolerance is increased metabolism due to enzyme induction

What is behavioral tolerance?

Behavioral tolerance is the adjustment of behavior to compensate for adverse effects (eg, broad-based gait or walking near wall in alcohol-dependent individuals)

What is cross tolerance?

Cross tolerance is physiologic tolerance to others of the same drug class or similar action. If you take a similar drug to something you've been taking a while, you'll probably be tolerant to the similar drug

What is reverse tolerance aka sensitization?

Reverse tolerance aka sensitization occurs when you take a drug for the first time. You will feel very strong effects to the drug taken

What is addiction?

Addiction is the habitual dependence on a substance or practice beyond voluntary control. Chronic drug/alcohol use co-opts normal reward functioning, leading to craving and loss of control or addiction

How do you treat addiction?

Cognitive behavioral therapy

What are some drugs to treat opiate addiction/withdrawal/overdose?

Methadone (to treat addiction), clonidine (to treat withdrawal), naltrexone (to treat overdose), buprenorphine (blocks the effects of other opiates)

What happens when you have a rapid removal of ethanol from your system?

Withdrawal symptoms

What do withdrawal symptoms look like in alcoholics?

Seizures, agitation, hypertension, tachycardia

What does disulfiram do?

Disulfiram can treat drinking problems. Every time you drink alcohol, you will feel an unpleasant reaction to alcohol. It's used in recovery programs that include medical supervision and counseling

What is bupropion (zyban)?

Bupropion is a nicotinic antagonist

What is varenicline (chantix)?

Varenicline is a nicotinic partial agonist

What are positive symptoms of schizophrenia? How is it caused?

Positive symptoms include hallucinations (often auditory) and delusions. The positive symptoms of schizophrenia are due to the increase of dopamine in the mesolimbic pathway

What are negative symptoms of schizophrenia? How is it caused?

Negative symptoms of schizophrenia include flattened affect, apathy, avolition, and anhedonia. The negative symptoms are caused by too little dopamine

What are the cognitive symptoms of schizophrenia?

Thought disorder, loose associations, incoherence ("word salad"), and sensorimotor gating deficits

What are typical antipsychotics?

Typical antipsychotics work by targeting D2 receptors. The problem with typical antipsychotics, when they block dopamine, they make the transmission signal go down. These people will report that they no longer experience positive symptoms, but their negative symptoms get exacerabted

Atypical Antipsychotics

These target serotonin (5-HTA) and dopamine receptors. These are good at treating both positive and negative symptoms

What are characteristics of 2nd generation antipsychotics (aka atypical antipsychotics)

1) 5-HT2A antagonism is more potent than D2 receptor antagonism

2) Beneficial effects on both positive and negative symptoms

3) Low (or absent) likelihood of extrapyramidal motor system effects (EPS)

What structures are in the extrapyramidal system?

Substantia nigra, caudate, putamen, globus pallidus, thalamus, red nucleus, and the subthalamic nucleus

If there were drugs that affected the extrapyramidal system, what side effects might occurs?

Tardive dyskinesia, akathisia, dystonia, oculogyric crisis, and parkinsonism

How does the striatum (extrapyramidal) circuits involve themselves in the basal ganglia?

1) Preparation and initiation of movement

2) Production of motor patterns, skills, habits

How does the putamen citcuits involve themselves in the basal ganglia?

Corticostriatal, striatal (direct and indirect), subthalamic loop (indirect), pallidothalamic, thalamocortical

How do you treat Parkinson's disease?

Dopamine agonist, MAO inhibitors, and NMDA antagonists