Lecture 22 - Drug Abuse Flashcards
Opiate
Morphine Dependence liability: +++
Psychostimulant
Cocaine, amphetamine and nicotine Dependence liability: +++
Psychotomimetic
LSD, Mesacaline, Cannabis Dependence liability: -
CNS depressants
Ethanol and Barbiturate Dependence liability: ++
Anxiolytics
Benzodiazepine Dependence liability: +
What is a classical antagonist of opiates?
Naloxone
What happens when mu receptor is stimulated?
Stimulate an opioid receptor with Morphine G protein coupled mechanism - negative effects upon 2 forms of adenylate Cyclase (reduces level of CAMP) CAMP has knock out effect on the activation of protein kinase A or certain protein kinases - reduce excitability of the target cell Longer term of Morphine; alteration in gene expression through changes of effects of CAMP response element binding proteins to the genetic material
The mu receptor is the most important in terms of what?
Abuse potential and development of tolerance
How does Morphine cause inhibition?
Increasing K+ conductance and by inhibiting adenylate cyclase activity - in turn reducing CAMP levels and phosphorylation of PKA
Drug-self administration
Skinner box so that a little lever protrudes into the chamber where the animal is placed and that is attached to a reservoir which is filled with substance of interest By pressing lever, the animal can deliver the drug via canular into region within brain
ICSS: intra-cranial self-stimulation
Small electrode is implanted into discrete brain region and pressing the lever will cause a small discharge of electrical current from that electrode
What does Morphine Increase?
Dopaminergic fell firing in VTA
What does Morphine mimic the effects of?
Endogenous Beta-endorphins
What can Morphine elevate levels of?
Dopamine through the use of GABAergic interneurons
What does intra-VTA Morphine Increase?
Lever pressing
What decreases lever pressing and basal dopamine release?
Blockade of mu receptors in VTA
What does blockade of dopamine receptors block?
Lever pressing
What are examples of Psychostimulants?
Cocaine and amphetamine
What are effects of psychostimulant?
Euphoria, behavioural excitement, reduced fatigue and anorectic
What are used of psychostimulant?
Anorectic, local anaesthetic and ADHD
What is an example of cognitive enhancer?
Metaphenidate
What effect does cocaine and amphetamine have?
Cause elevation in release of dopamine
What do cocaine and amphetamine influence ?
Dopaminergic nerve terminal as they are both indirect sympathomimetics
What does cocaine block?
Dopamine uptake transporter
What is dopamine inactivation mechanism?
Re-uptake and subsequent breakdown of catechol-methyl transferase or mono-amine oxidase
What are the effects of cocaine and amphetamine?
Tolerance to euphoric effects - dose escalation Withdrawal symptoms Highly addictive with strong re-inforcement properties Psychotic reactions
What does psychotic reaction demonstrate?
The phenomenon of sensitisation
When is the main effect of amphetamine seen?
When administered into nucleus accumbens
When is the main effect of cocaine seen?
Administered into frontal cortex
What are psychostimulants?
Compound that are characterised by changes in behavioural arousal and excitation
What are psychotomimetic compound?
Component that alter perception significantly
Cause profound hallucinogen
What influences the serotoninergic system?
Synthetic compound: LSD
Mescaline
What treats anxiety?
CNS depressant
Anxiolytic drug
What does opiates and psychostimlant that have profound dependence liability comprise of?
Psychological and physiological component
What was barbiturate used for?
Treatment of anxiety and anxiety related conditions
