Biological basis of addiction and schizophrenia Flashcards
What is the definition of substance abuse and how does this differ from dependence/addiction?
Frequent/excessive use of substance, damages relationships and daily functioning
Addiction is when substance taking becomes COMPULSIVE, driven to take it every day even when enjoyment no longer present; life becomes centred around it and there are tolerance/withdrawal effects experienced
What demonstrates the compulsive nature of substance addiction?
Persistent desire and unsuccessful efforts to cut down or control the substance use
Continued use despite persistent/recurrent interpersonal problems caused/exacerbated by substance effects
Substance use continued despite knowledge of the persistent/recurrent problems
What are the 3 stimulant drugs and their underlying pharmacology?
Amphetamine and cocaine - increase levels of dopamine in synapse
Nicotine - agonist at ACh receptors
What are the 3 depressant drugs and their underlying pharmacology?
Morphine and heroin - agonist at opiate receptors
Alcohol - biphasic i.e. stimulant first then depressant, having a variety of effects at dopamine, glutamate and GABA receptors
What are the 4 hallucinogens and their underlying pharmacology?
LSD - Agonist at 5HT receptors
Phencyclidine - Antagonist at glutamate receptors
Cannabis - Mixed effects at cannabinoid receptors
Ecstasy - Variety of effects at dopamine, glutamate and GABA receptors
What has been suggested regarding the mechanisms by which all the drug types become addictive?
All share the ability to increase dopamine release in the nucleus acumbens (terminal region of mesolimbic pathway), a pathway important in reward and motivation - dopamine is released here for natural rewards and animals will work to receive these, or elec stimulation that produces the same sensation (actually neglect eating to keep pressing a lever for the stim)
Addictive drugs essentially hijack this pathway and drive motivation towards drug-taking behaviours
What is the mesolimbic pathway?
Dopaminergic pathway projecting from the ventral tegmental area in midbrain to nucleus acumbens in forebrain
Even addictive behaviours activate this pathway, still very much biological
Dysfunction of this pathway is implicated in schizophrenia too
In addition to activation of the dopaminergic mesolimbic pathway, how is addiction established?
Behaviours associated with taking the drug become addictive themselves via classical conditioning - behaviour becomes conditioned stimulus for feelings of reward and motivation, so someone may be motivated to take a drug simply when exposed to an associated stimulus (common reason for relapse in addicts)
What are the 3 types of schizophrenia symptoms?
Positive, negative
Cognitive - more to do with frontal cortex than mesolimbic pathway; disturbance of attention, memory and executive function
What are typical antipsychotics effective for>
Mainly treating positive symptoms, not negative or cognitive
Why are typical antipsychotics not that effective?
Only help around 50% of patients after 10 yrs of treatment
Only help positive symptoms
Associated with severe extrapyramidal motor side effects
Other side effects include sedation, hypotension and actually enhancement of negative symptoms
Significant threat to compliance
Why are atypical antipsychotics slightly better?
Minimal motor side effects
Effective at treating negative and cognitive symptoms
How do atypical antipsychotics work?
Mixed pharmacology, interacting with NT systems other than dopamine - critical effects seem to be mediated through dopamine antagonists and serotonin antagonists
Suggests role of serotonin but again unlikely to be core deficit - drugs still don’t treat everyone, so dopamine and serotonin are more likely downstream effects, treating symptoms rather than cause
What 3 drugs produce symptoms similar to those of schizophrenia?
Amphetamine - Increases dopamine and produces positive symptoms (dopamine theory)
LSD - Serotonin agonist and produces positive symptoms; so serotonin involved but may reflect its widespread modulatory role in brain wherein disruption causes failures of normal functioning of other systems
Phencyclidine - Glutamate antagonist and causes positive, negative and cognitive symptoms, also enhancing symptoms in patients
What is thought to be the core underlying neurochemistry of schizophrenia?
Cortical glutamate dysfunction, leading to downstream dysregulation of glutamate-mediated control of dopamine function
Glutamate-targeting drugs are yet to be developed - most widespread excitatory NT so any therapeutic effect would carry risk of widespread side effects and potential excitotoxicity
