L6: Neurotransmission: Drug abuse Flashcards
How is addiction defined by Orford, 1985?
- loss of control over a form of behaviour pleasurable to most people
- an excessive appetite
What drug abuse did Gardner, 1964 struggle with?
Alcohol
- a separation of liking and wanting….
Which drug was used to keep soldiers awake for longer?
Philopon = methanphetamine
- resulted in somatosensory hallucinations - tics under the skin
Which neurotransmitter receptors do nicotine, the psychoactive component od tobacco, act on?
- acetylcholine receptors
- peripheral NS
- CNS
2 broad acetylcholine receptors…
- Nicotine specific to nicotine
- Muscarinic - specific to an alkaloid muscarine
Which neurotransmitter receptors do alcohol act on?
- GABA-A + GABA-B receptors
- opioid receptors
Which neurotransmitter receptors do opiates act on?
- opioid receptor
- V selective
- help decrease sensation of pain
Which neurotransmitter receptors do MDMA (ectasy) act on?
- serotonin 2A
- SSRI
Which neurotransmitter receptors do cocaine act on?
- Dopamine transporter
Which neurotransmitter receptors do amphetamine act on?
- dopamine –> releases them
Which neurotransmitter receptors do Barbiturates act on?
- modulates GABA-A receptor
Which neurotransmitter receptors do cannabis act on?
- Cannabinoid CB1 receptor
What does the place preference task show about receptors and addiction?
- Rats put into a box with two compartments they can go between
- One side = given morphine, other a non-active control
- transgenic mouse without opioid receptors fails to learn task
- normal = greater preference for morphine room
- middle = equal preference for the different rooms
What are some issues with the place preference task?
- anatomies of humans and mice are different
- missing receptor may be important for the development of mice = so not reflective of adult mice?
- an adaptive response?
Give a run down on cocaine
- once was in coca-cola
- obtained from coca-shrub
- local anaesthetic resembling lidocaine
How do lidocaine and cocaine act as anaestheitcs?
- block voltage-gated sodium channels
= no AP can be produced so no pain is reaching the NS
Give a run down on amphetamine
- first synthesised in 1887
- psychoactive effects discovered 1920s
- clinical use: ADHD, narcolepsy
- widely used as a decongestant
- -> Benzedrine inhaler
What are cocaine and amphetamines effects on the dopamine neurotransmitter system?
Cocaine:
- Blocks dopamine transporters (DAT)
Amphetamine:
- enhances dopamine release and reduces re-uptake
- -> amphetamine is transported into the pre-synaptic terminal - displaces dopamine from vesicles leading to synaptic release
both increasing levels of dopamine at the synapse
- making it difficult to distinguish
Describe the transmission of information in the dopamine neurotransmitter system
- depolarisation in pre-synaptic neuron = release dopamine
- Acts post-synaptically
- Taken back-up by the dopamine transporter (DAT)
- Then reincorporated into vesicles by the vesiclar monoamine transporter (VMAT)
Name a few of the many psychoactive compounds in cannabis
- ∆9-Tetrahydrocannabidol (∆9-THC) - major psychoactive component
- Cannabidiol - quite different pharmacologcal properties
- Canabigerol - a precursor but with it’s own activity as well
Which cannabionoid receptors are found where in the brain periphery?
- CB1 - mostly CNS
- CB2 - mostly peripheral
- TRPV1 - capsaicin (chilli) also acts here
What are the endogenous neurotransmitters of cannabis?
- Anandaminde
2. 2-arachidonoglycerol (2-AG)
Who is John Huffman?
- synthesised a range of compounds
- some with high affinity + efficacy
- Rimonabant = fails appetite suppressant
What are the properties of ∆9-THC?
Partial agonist:
- high affinity
- low efficacy
What does affinity and efficacy mean?
affinity:
- How well the drug binds to its receptors
Efficacy:
- How well it does its job (effect)
What is the difference between Full, partial agonist and antagonists?
Full agonist:
- produces maximal stimulation of the target at higher doses + high efficacy
Partial agonist:
- produces smaller effect vs full, even at high higher doses
- can compete w/ full, reducing its effect
- moderate efficacy
Antagonist:
- produces negligible effect (low efficacy), regardless of dose
- by competition at receptors, reduces effect of partial + full agonists
When a partial agonist or antagonist are administrated at the same time as a full agonist, how does it effect the full agonist?
- reduction in effect
What did Grant et al 1996 find when cocaine abusers were asked to rate craving for cocaine while observing images of either neutral or cocaine associated objects?
- cravings greatly increased while the ppt observed cocaine-associated cues
- Blood flow to the PFC + medial temporal cortex greatly increased
- increased activation in ventral striatum + other basal ganglia structures
(PET - radioactive glucose metabolism)
What did Bern 2004 find suggesting the meso-limbic dopamine system may also be activated by a wide variety of natural rewards - even those with a strong cognitive element?
- imaging study
- ‘funny’ cartoons evoked laughter
- activation of =
- motor areas
- other cortical areas
- central striatum (part of the mesolimbic dopamine system)
What are the different way for treating drug addiction?
- substitue drug with one that has less rewarding properties
- - heroin w/ methadone - Block effects of a rewarding drug by treating w/ an antagonist/ partial agonist
- Naltrexone may also be useful in reducing heavy drinking
- Behavioural strategies?
