Drugs of abuse (Nbio) Flashcards
What pathways are involved?
- Dopamine and serotonin
What are the functions of the dopamine pathways?
- Reward
- Pleasure, Euphoria
- Motor function
- Compulsion
- Perserveration
What are the functions of the Serotonin pathways?
- Mood
- Memory processing
- Sleep
- Cognition
What is the mesolimbic dopamine pathways?
- Midbrain ventral tegmental area (VTA) dopamine neurons innervate the nucleus accumbens, part of the limbic system controlling emotion, pleasure, reward and goal-directed behaviour.
- Overactivity in this pathway contributes to psychosis, delusions and hallucinations: The positve symptoms of schizophrenia.
- Involved in producing reward and pleasure to encourage to do - Dopamine pathwyas are responsible
What are the brain reward pathways?
- Common feature many drugs of abuse increase dopamine release in Nuc Acc:
* Opiates, opiods, Nicotine, Amphetamine, Cocaine etc etc - Others drugs enhance 5-HT function (innervate nuc.ACC)
* LSD
* Ecstacy
3.Others block N-methyl-D-Aspartate receptors
* NMDA antagonists (Ket)
Explain a reward experiment with rats
- Activity in VTA dopamine neuronal pathways is associated with reward
- Rats will self admin rewarding drugs and using microelectrodes
- Activity can be recorded from dopamine neurons in VTA
- (rats press a lever that delivers intavenous cocaine)
How does a difference in reward vs expected reward change things?
- A reward that is better than predicted elicits stronger neuronal activation
- VTA DA neurons respond to unpredicted reward by a phasic short lasting burst of activity which results in DA release from nerve terminals in Nuc.Acc and frontal cortex
What is Microdialysis?
- A technique that allows NT release into the extracellular fluid to be measured in conscious animal brain
What effects do Amphetamines, cocaine, Nicotine and Ethanol on dopamine?
- All drugs enhance DA in the VTA dopaminergic
- Leading to reward
How do drugs of abuse enhance release of dopamine?
What is the common key feature of drug of abuse?
The faster, higher and more reliable the elevation in brain dopamine levels, the greater the reward (euphoria) and more likely addiction will occur
- Formulation is a factor affecting absorption rate - Kinetics
- Intravenous heroin ‘more addictive’ than methadone by mouth
- Inhaling cocaine greater reward than chewing coca leaves
- Smoking cigs greater reward than chewing tobacco
Describe some drugs and their dependance reliability.
- Narcotic analgesics: Morphine + Heroin
* Both v.strong degree of dependace liability - General CNS depressants: Ethanol, Barbiturates, Cannabis
* First 2 strong, cannabis weak - Anxiolytic: Benzodiazepines
* Strong
4.Psychostimulants: Amph, Cocaine, caffeine, Nicotine, Ecstacy
* Strong,V.S, Weak, V.S, Absent?
5.Psychedelic: LSD
* Weak/absent
What are opiods?
- Morphine/Heroin
- All agonists at G-protein-coupled opiod receptors
- Red NT release
- Cause: Analgesia, euphoria, pve reinf, Respiratory depression
Acute effects
* Euphoria, tranq, miosis
Chronic Effects
* Constipation, depression, insomnia, dependence
* Anhedonia and tolerance
What are withdrawal signs of Opioids?
- Craving, restlessness, insomnia, dependence
- Cold flashes with goose bumps
- Major symp 48-72 hours after last dose
What is cocaine?
- Alkaloid
- Inc catecholamine (DA) NT function by prev DA re-uptake
- Overactivity of symp system at higher doses: Hypertension, tachycardia, dilated pupil, palpitations
- Crack-smoked = V.rapid dependence
- Little tolerance
- Little physical dependence
- Strong psychological dependence
