Bio psych - Drug Addiction

Lecture idk actually

Drugs

Chemical substances which interact with the biochemistry of the body:

• Inhibit or reinforce enzyme activity

• Block or activate receptors

• Interact with neurotransmitters or hormones in other ways

• Attack “invaders” (e.g. antibiotics)

What are psycho-active drugs?

• Any chemicals that influence the way we feel or act

• Usually they interact with the nervous system and/ or the endocrine system

• Mostly, they act at synapses (among other places)

Agonist vs. Antagonist

At the synapse level (effect on post-synaptic cell):

• Agonist; mimics action of the neurotransmitter

• Antagonist; blocks action of the neurotransmitter

At the receptor level (effect on receptor):

• Agonist; mimics action of the neurotransmitter

• Antagonist; blocks action of the neurotransmitter

Possible sites of drug action

• If a drug is an antagonist on the presynaptic receptors - it results in an increase in neurotransmitter - makes it an agonist at the synaptic level

• If its agonist at the receptor level (stimulates the receptors prevents release of neurotransmitter) - it will be antagonist at the synaptic level as it prevents the release of neurotransmitters

Pharmacokinetics: Intake

Many routes:

• Digestive tract

• Respiratory tract

• Through skin

• Through mucous membranes

• Intravenous injection (directly into the blood)

• Intramuscular injection (into the muscles)

• Subcutaneous injection (under the skin)

What is the slowest uptake route?

Digestive Tract

Pharmacokinetics: Distribution

• Bloodstream goes all across the body

• Water-soluble molecules can be directly dissolved in the blood, but do not pass through cell membranes

• LIpid-soluble molecules need carriers to transport them through blood, but can pass directly through cell membranes

Blood-Brain Barrier

• Around most of the body the capillaries have gaps that permit the free flow of substances into and out of the blood

• In the brain, these capillaries do not have these gaps, preventing these substances from entering - unless the toxin or drug is fat soluble, as their membrane is made of fat (phospholipid bilayer), allowing entry into the brain - despite their difficulty in transporting in the blood

• In order to be psychedelic it almost has to be fat soluble

Pharmacokinetics: Elimination

• All drugs are eventually eliminated from the body:

  • By chemical break down (by enzymes)

  • By excretion (in urine)

• Some drugs can be stored in the body for a long time (e.g. lipid-soluble drugs in fat tissue)

• Biological Half-Life can vary from minutes to weeks

Biological Half-Life

• The time it takes for the drug to go from peak concentration to half concentration

• Shorter Half-Life means it can get to half quicker

• Longer means it takes longer to get to half

Typically, more lipophilic drugs have…

Longer Half-Life than less lipophilic drugs

Physical Dependence: Drug Tolerance

In tolerant subjects, a greater dose is required to produce the same effect

• Body maintains homeostasis

• Mechanisms:

  • Metabolic tolerance (better elimination of the drug)

  • Functional tolerance:

    • Change in receptor numbers

    • Change in receptor sensitivity

    • Change in intra-cellular cascades

Tolerance leads to withdrawal effects - the tolerance mechanisms are still there if the drug goes away

• Opposite effects of the drug = withdrawal effects

• Results in physical dependence on the drug - they now take the drug to prevent the withdrawal effects

Tolerance is Context Dependent

• Overdosing is easier in novel surroundings

• Withdrawal symptoms also occur in familiar settings - context (like your house) can trigger withdrawal symptoms

• Possibly a reason for relapsing

“Psychological” Drug Dependence - Operant Conditioning

• Stimulus results in increase in behaviour based on a reinforcement system

Intra-Cranial Self-Stimulation

• An operant Chamber with a lever, used in studying the effects of reinforcing brain stimulation

  • Rats activate lever, which activates the reinforcement part of their brain, which results in an increase in the behaviour

Major Brain Subdivisions

Forebrain

• Telencephalon

• Diencephalon

Midbrain

• Mesencephalon

Hindbrain

• Metencephalon

• Myelencephalon

Mesotelencephalic Dopamine System (?)

• Ventral tegmental area

• Nucleus accumbens

Involvement of Dopamine in reward

• Dopamine levels increase in the Nucleus Accumbens

How do you test whether dopamine release is causally involved in the rewarding effect of intracranial stimulation?

Block the action of dopamine whilst stimulating

Reward: Pleasure or…..?

• Dopamine is released with punishing stimuli as well

• Overtrained rats do not release dopamine upon reward

• Dopamine blockers make rats work less hard for food, but they still enjoy it

Dopamine doesn’t seem to be related to pleasure

Alternate hypothesis: SEEKING or WANTING

• Dopamine release is not the cause of enjoying something

• If you increase dopamine animals will start exploring more

• It also drives animals to repeat something, even if that thing is not pleasurable

“Psychological” Dependence

• When drugs directly interact with the brain’s reward system

• Addit will crave drugs, even while disliking their effects

Cocaine increases Dopamine levels

• Cocaine and Amphetamines increase the amount of dopamine even when directly injected into the Nucleus Accumbens

Intracranial Drug Self-Administration

• The rat has a catheter(?) - (like a lil needle thing) injected into it and it pesses the lever to self-inject the drug, from an infusion pump, either in a particular area of the brain or into general circulation

Summary

• Different Drugs have different pharmacokinetics

• Physical drug dependence is due to drug tolerance

• The Ventral Tegmental Area and Nucleus Accumbens are involved in the “reward” or “seeking” system in the brain

• Psychological dependence works through this Mesotelencephalic dopamine pathway