![Page 1: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/1.jpg)
Drug addiction – learning gone wild?
Dr Stuart McLaren
MRCPsych. Phase 1 Psychopharmacology module
15.02.13
![Page 2: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/2.jpg)
Structure of session
• Introduction• Dopamine and the mesolimbic reward systems
in the brain• Systems modulating the mesolimbic system
– GABA– Opioids– Glutamate
• Tolerance and withdrawal• Substitution or maintenance treatments
![Page 3: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/3.jpg)
Substance dependence (3+ in last year)
• Strong desire or sense of compulsion to take alcohol
• Difficulties controlling alcohol-taking behaviour• Physiological withdrawal state when alcohol is
stopped or reduced• Evidence of tolerance• Neglect of alternative pleasures or interests (so-
called ‘salience’)• Persisting with alcohol use despite harmful
consequences
![Page 4: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/4.jpg)
Phases of treatment 1
Substitution therapy
Opiates – methadone, buprenorphine, heroin
Stimulants – controversial
Alcohol – not generally used
Benzodiazepines - controversial
![Page 5: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/5.jpg)
Phases of treatment 2
Detoxification
Opiates – dose methadone or buprenorphine, lofexidine
Stimulants – none, symptomatic
Alcohol – benzodiazepines, anticonvulsants, ? acamprosate
Benzodiazepines - dose
![Page 6: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/6.jpg)
Phases of treatment 3
Relapse prevention
Opiates – naltrexone
Stimulants – none
Alcohol – acamprosate, naltrexone, disulfiram, baclofen
Benzodiazepines - none
![Page 7: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/7.jpg)
Molecular targets of drugs of misuse
Cocaine and amphetaminesPrimary target Dopamine transporter
(DAT)
Main acute effects Dopamine
Adaptions DA-ergic activity, glutamatergic activity
Other actions Local anaesthetic, includes 5-HT, ?NA release
![Page 8: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/8.jpg)
Molecular targets of drugs of misuse
Opiates
Primary target Mu () opiate receptors
Main effects ? Dopamine
Adaptions sensitivity of MOR, upregulation of NA activity
Other actions Kappa () and delta () opiate receptors
![Page 9: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/9.jpg)
Molecular targets of drugs of misuse
Alcohol
Primary target GABA/glutamate
Main effects GABA / glutamate
Adaptions GABA sensitivity, upregulated NMDA glutamate
Other actions Many other systems reward, opioid, GABA-B, dopamine
![Page 10: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/10.jpg)
A simplified model of addiction
![Page 11: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/11.jpg)
Model proposing a network of four circuits involved with addiction
![Page 12: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/12.jpg)
Reward (or reinforcements) – objects or events that make us come back for more
![Page 13: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/13.jpg)
Intracranial self-administration of morphine in a rat
![Page 14: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/14.jpg)
Activation of the reward pathway by electrical stimulation
![Page 15: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/15.jpg)
Activation of human striatum by various rewards
![Page 16: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/16.jpg)
Brain images at different times after drug administration
![Page 17: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/17.jpg)
The role of dopamine in reward circuits
![Page 18: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/18.jpg)
Dopamine (D1-like) receptor structure
![Page 19: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/19.jpg)
Dopamine circuits in the brain
![Page 20: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/20.jpg)
Mechanism of drug-related increase in dopamine activity
• Block of dopamine transporter (DAT) in NAcc e.g. Cocaine
• Reuptake blockade plus direct DA release from terminals e.g. Amphetamine
• Increased DA neuronal firing via disinhibition in the VTA e.g. Alcohol, opiates, nicotine
![Page 21: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/21.jpg)
Dopamine binding to receptors and uptake pumps in the nucleus accumbens: the action of cocaine
![Page 22: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/22.jpg)
Key structures and connections involved in addiction
Lingford-Hughes A et al. Br Med Bull 2010;96:93-110
© The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]
![Page 23: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/23.jpg)
fMRI during cocaine intoxication vs. saline infusion
![Page 24: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/24.jpg)
Low level of dopamine D2 receptors in methamphetamine abusers
![Page 25: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/25.jpg)
Where substances of abuse interact with the dopaminergic mesolimbic system and its key modulators.67.
Lingford-Hughes A et al. Br Med Bull 2010;96:93-110
© The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]
![Page 26: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/26.jpg)
PET study of the effect of chronic drug exposure
![Page 27: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/27.jpg)
PET scan of raclopride binding in the striatum of cocaine and methamphetamine
abusers
![Page 28: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/28.jpg)
Axial sections with PET showing DA D2 receptors in non human primates
![Page 29: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/29.jpg)
The action of bupropion
• Atypical antidepressant • Used in treatment of nicotine dependence,
detoxification and relapse prevention• DA and NA reuptake inhibitor, antagonist at
nicotinic acetylcholinergic receptor• Meta-analysis of 49 trials > effective than
placebo• Action independent of antidepressant effect
![Page 30: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/30.jpg)
Bupropion blocks the DAT
![Page 31: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/31.jpg)
Conventional mechanism of action of disulfiram in relapse prevention
![Page 32: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/32.jpg)
Other action of disulfiram, DA levels
![Page 33: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/33.jpg)
Other neurotransmitter systems that modulate the mesolimbic system
GABA
![Page 34: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/34.jpg)
GABA-A receptor structure
![Page 35: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/35.jpg)
Alcohol’s effect on neurotransmitter systems involved in the brain’s reward pathways
![Page 36: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/36.jpg)
Action of the brain’s GABA system in the presence of alcohol
![Page 37: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/37.jpg)
Action of the brain’s GABA system after chronic alcohol exposure
![Page 38: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/38.jpg)
The action of baclofen
• GABA – B agonist• Licensed for muscle spasm• Increases tonic inhibition of mesolimbic DA
neurons• Reduces DA release in the ventral striatum• Reduces drug seeking and consumption of
alcohol, cocaine and nicotine• Reduces relapse in alcohol dependence, not yet
mainstream
![Page 39: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/39.jpg)
Other neurotransmitter systems that modulate the mesolimbic system
Opioids
![Page 40: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/40.jpg)
The neuroactive peptide beta-endorphin
![Page 41: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/41.jpg)
Structure of diamorphine
![Page 42: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/42.jpg)
Opioid receptor structure
![Page 43: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/43.jpg)
Opioid receptor function
• Mu (MOR) analgesia, respiratory depression, pupillary constriction
• Kappa (KOR) dysphoria, depersonalization, sedation
• MOR + DOR activation of reward
• KOR attenuates reward
![Page 44: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/44.jpg)
MOR receptors are present in the VTA on the GABA inhibitory neurons
![Page 45: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/45.jpg)
Opiates binding to opiate receptors in the nucleus accubens: increased dopamine
release
![Page 46: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/46.jpg)
The action of naltrexone
• Non-selective opiate antagonist• Increases activity in the OfCx (? control)• Blocks reward associated with MOR in the VTA
via preventing increased DA activity• Used both in opiate and alcohol dependence
relapse prevention• May be useful in some impulse-control disorders
such as pathological gambling
![Page 47: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/47.jpg)
Other neurotransmitter systems that modulate the mesolimbic system
glutamate
![Page 48: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/48.jpg)
Receptors modified by alcohol
![Page 49: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/49.jpg)
Glutamate receptor structure
![Page 50: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/50.jpg)
Alcohol’s effect on neurotransmitter systems involved in the brain’s reward pathways
![Page 51: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/51.jpg)
Alcohol’s effect on endogenous opioids and the mesolimbic DA system
![Page 52: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/52.jpg)
Activation of the brain’s glutamate system
![Page 53: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/53.jpg)
Activation of the brain’s glutamate system with alcohol
![Page 54: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/54.jpg)
The action of acamprosate
• Used in alcohol relapse prevention• Said to be ‘anticraving’ in action glutamatergic activity GABA–ergic activity• Partial agonist at the NMDA receptor in Nacc• May be neuroprotective during alcohol
withdrawal
![Page 55: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/55.jpg)
Tolerance and withdrawal
Two sides of the same coin
![Page 56: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/56.jpg)
Neurotransmitters implicated in substance withdrawal
• ↓dopamine ‘dysphoria’• ↓serotonin ‘dysphoria’GABA -A anxiety, panic• ↓neuropeptide Y anti-stress• ↑dynorphin ‘dysphoria’• ↑CRF stress• ↑noradrenaline stress glutamate hyperexcitability
![Page 57: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/57.jpg)
Actions of the brain’s GABA system in chronic alcohol exposure and
withdrawal
![Page 58: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/58.jpg)
Action of the brain’s glutamate system after chronic exposure to alcohol and during
withdrawal
![Page 59: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/59.jpg)
Alcohol withdrawal
• Benzodiazepines GABA-ergic function• Anticonvulsants e.g. Lamotrigine (glutamate
release inhibitor) • Acamprosate NMDA hyperactivity, and may
have neuroprotective effects (i.e. reduced cell death)
![Page 60: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/60.jpg)
Opiate withdrawal
Lofexidine and clonidine
• Alpha-2 receptor agonist• Reduces noradrenergic overactivity associated
with opiate withdrawal (MOR are inhibitory and NA activity upregulated in ascending brain pathways)
• Main site of action the locus coeruleus• May cause hypotension, clonidine>lofexidine
![Page 61: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/61.jpg)
Substitute or maintenance treatment
A very good evidence base but still controversial with some
![Page 62: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/62.jpg)
Opioid maintenance therapy
Methadone• Full MOR agonist• Receptor occupancy ~ 32%• Long acting (half life ~ 24 hours)
Buprenorphine• Partial MOR agonist, KOR antagonist• High affinity
• Long acting (half life > 24 hours)
![Page 63: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/63.jpg)
Novel mechanisms
Stress/antistress systems
Glial cells
![Page 64: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/64.jpg)
The effect of alcohol on reward and stress circuits in the brain
![Page 65: Drug addiction – learning gone wild? Dr Stuart McLaren MRCPsych. Phase 1 Psychopharmacology module 15.02.13](https://reader030.vdocuments.site/reader030/viewer/2022032702/56649f435503460f94c63809/html5/thumbnails/65.jpg)
Astrocyte function