Week 6 PSY 383 Midterm - Caffeine/Nicotine & Antidepressants

What is an antidepressant? 

A class of psychoactive drugs primarily used to treat mood (affective) disorders such as depression and anxiety

Influence neurotransmitter systems 

• Serotonin, norepinephrine, dopamine 

Learned Helplessness

• Dogs that experience uncontrollable shocks earlier did not try to escape, even when escape was easy. 

• Uncontrollable stress leads to inaction and depressive symptoms 

Stress and Depression 

• Highly elevated cortisol levels in depressed patients 

• What maks psychological stressors more stressful? 

  • No outlets

  • Feeling of no control over what is happening 

  • No predictability as to when it is occurring 

History

Accidental Discoveries 

A new drug for tuberculosis 

• Discovery of the first MAOI

A new drug for schizophrenia 

• First tricyclic antidepressants 

Norepinephrine theory of depression 

In the 1950s and 60s, depression was believed to be caused by low norepinephrine levels 

Tricyclics and MAOIs

• Both drug classes increased norepinephrine leading to improved mood

Blood pressure drugs 

• Medications like reserpine which reduce norepinephrine often caused depressive symptoms 

Problems with the NE theory 

NE was thought to be a key regulator of mood

• Researchers started to find it was more specifically involved in arousal, attention, and the body’s stress response 

- Dopamine found to be more important part of the “pleasure pathway” 

- NE is synthesized from broken down dopamine 

The rise of SSRIs

• (1987) Prozac became the first widely used selective serotonin reuptake inhibitor (SSRI) 

• Fewer Side Effects 

Serotonin Theory of Depression 

SSRIs inhibit recycling of serotonin which increases serotonin levels

• Results in symptom relief from depression

Tryptophan depletion (precursor to serotonin) leads to decreased levels of serotonin

• Results in increased symptoms of depression

Dopamine and Serotonin 

Dopamine systems are linked to guiding action and motivation 

Serotonin systems are linked to evaluating whether we can expend that energy 

Integrated Neurochemistry Theory

Dopamine - Motivation 

Norepinephrine - Arousal 

Serotonin -Aversive 

Neurotransmitter Clearance 

Reuptake - Neurotransmitters are reabsorbed into the presynaptic neuron through transporter proteins

Enzymatic Degradation - Enzymes break down neurotransmitters in the synaptic cleft

MAOIs Mechanism of Action 

Inhibition of Monoamine Oxidose (MAO) enzyme 

• Bind irreversibly to the enzyme, meaning the effects last until new enzymes are produced (about two weeks)

Increase levels of all three major monoamines (sero., nore. , dopa.) 

MAOI Side effects 

 MAOIs can cause dangerous spikes in blood pressure if combined with foods like aged cheese, cured meats, and certain alcohol

Tricyclics Mechanism of Action 

Non-Selective in their action 

• Contributed to their diverse effects in high side effect profile 

Tricyclics Side Effects 

Histamine blockade effects 

• Can cause significant drowsiness and fatigue 

SSRIs mechanism of action 

Selective Serotonin Reuptake Inhibition

• Block the reabsorption (reuptake) of serotonin into the presynaptic neuron increasing serotonin availability in the synapse

• Selective Action 

  • Fewer side effects related to other neurotransmitter 

Work primarily on the 5HT-1A (Inhibitory)

Activating 5HT-1A 

Activating the 5HT-1A system leads to an inhibitory effect on subcortical emotional processes

• Leads to reduced emotional intensity

Sexual Side Effects 

• Inhibition of drive and pleasure via the 5HT-1A system is thought to contribute to the sexual dysfunction often reported by patients 

SNRIs and Wellbutrin 

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Block the reuptake of both serotonin and norepinephrine selectively

Wellbutrin - (norepinephrine-dopamine reuptake inhibitor NDRI) 

• Block the reuptake of both dopamine and norepinephrine selectively

Delayed Onset  

Antidepressants, including SSRIs, SNRIs, TCAs, and MAOIs, typically take 2-4 weeks before patients begin to experience significant mood improvement

• Side effects can begin immediately

Antidepressant Withdrawal 

Stopping antidepressants, particularly SSRIs and SNRIs, can lead to significant withdrawal symptoms, often referred to as discontinuation syndrome

What is a stimulant?

A substance that increases brain and

nervous system activity

• Effect

 They enhance arousal and alertness,

leading to increased energy, focus,

and reduced fatigue

• Medical Uses

 Often prescribed to treat attention

deficit hyperactivity disorder (ADHD),

narcolepsy, and sometimes depression

Sympathetic Nervous

System (SNS)

• Controls “fight or flight” and readies the body for stress

• Raises heart rate, opens airways, releases energy, boosts alertness

• Stimulants target the SNS, activating its

  arousing effects and increasing

  physiological readiness

How do Stimulants work?

• Dopamine

 Modulatory neurotransmitter involved in

motivation and reward

• Norepinephrine

 Modulatory neurotransmitter involved in

alertness and arousal (prepares the body

for action)

• Stimulants primarily increase the activity of

dopamine and norepinephrine

 Increases neuronal activity in arousal

pathways related to focus, motivation and

reward

Common Classes of Stimulants

Caffeine and nicotine

 Very different mechanisms of action than

other stimulants

Long Term Effects of Stimulants

• Cognitive Impairment

  • decreased ability to focus overtime

• Mental health issues

  • increased anxiety

• Physical Issues

  • elevated blood pressure

Caffiene History (Europe)

Penny Universities (1700s)

 For the price of a penny, one could buy a cup

of coffee and engage in lively discussions

about politics, science, and philosophy

Absorption and Distribution

Absorption

 Caffeine (like alcohol) is lipid and water

soluble meaning that it is rapidly absorbed

into the bloodstream

 Very little first pass metabolism effect (nearly

100% of the dose enters circulation)

Metabolism and Elimination (Caffeine)

Primarily metabolized in the liver and

produces various active metabolites

 Paraxanthine (80%) - Releases free fatty

acids for energy

Mechanism of Action

Adenosine

 A neurotransmitter that builds up in

the brain throughout the day

creating feelings of drowsiness and

relaxation

 Signal to the brain to start resting

• Caffeine is an adenosine antagonist

 Blocks adenosine receptors and

prevents it from binding

 Prevents the brain from knowing

how tired it should be

Dopamine and

Norepinephrine

Caffeine indirectly increases dopamine and

norepinephrine activity by reducing

adenosine-mediated inhibition

 Adenosine build up typically slows down

Dopamine and Norepinephrine release

• Dopamine release also tags the increased

  focus and mood to the drug

   Creates cravings and leads to addiction

Withdrawal

 Higher levels of adenosine

receptors results in heightened

fatigue and difficulty concentrating

Nicotine History

Indigenous Use of

Tabacco

 Began over 6,000 years ago with Native

American cultures across the Americas

 Sacred Plant:

 Used in ceremonies to communicate with

spirits

 Smoke carried prayers and connected the

earthly to the divine

 Symbolized unity during important rituals

• Promoted as a cure-all

   Jean Nicot, after whom nicotine is

  named, sent tobacco to the French

  royal family as a treatment for migraines

The Cash Crop That

Built Colonies

Demand for tobacco in Europe fueled the

colonization of North America and

contributed significantly to the

transatlantic slave trade

Absorption & Distrubution (nicotine)

• Smoking/Vaping is the most common route

 Nicotine is quickly absorbed through the

lungs, reaching the brain in 7-10 seconds

• Nicotine is lipophilic, allowing it to easily

  cross cell membranes and the blood-brain

  barrier (BBB)—reaching the brain in under

  10 seconds

  

What is

Acetylcholine?

• Primary Neurotransmitter for Movement

 Acts at the neuromuscular junction,

directly enabling muscle contractions

and voluntary movements

• Cognitive Flexibility and Motor Coordination

  • Optimizes responses to changing

    environments and enables goal-

    directed movement

• Integration with Dopamine

   Interacts with dopamine to balance

  motor control and motivation

Nicotine Mechanism of Action

Acetylcholine (ACh) Agonist

 Mimics acetylcholine (ACh) by binding

to nicotinic acetylcholine receptors

(nAChRs) found in the brain and body

 Excitatory effect

 Activates neurons, making them more

likely to fire and send signals

• Receptors are found in both the brain and

body : Activates regions in the brain that

boost alertness and focus & Activates areas in the body that lead

to increased heart rate and blood

pressure

The Connection to Dopamine

Direct Dopamine increases from

Nicotine

 Dopamine neurons in the Ventral

Tegmental Area (VTA - reward

pathway) have nACh receptors

 Nicotine activation leads to an

increase in Dopamine release

 Indirect Dopamine increases from

Nicotine

 Reduces GABA in the VTA which

typically inhibits Dopamine release,

results in more dopamine

 Increases Glutamate activity in the

VTA which also increases Dopamine

Addiction

• Nicotine becomes highly reinforced

because of its rapid onset and the massive

release of Dopamine it causes

 The fast action of nicotine—reaching the

brain in 7-10 seconds—creates a strong

link between smoking behavior and

reward

• Cue-Induced Cravings

   The combination of dopamine,

  glutamate, and other neurotransmitters

  helps form strong associations between

  smoking and environmental cues