LECTURE 1- INTRODUCTION TO PSYCHOPHARMACOLOGY Flashcards
what is psychopharmacology the study of?
it is the study of the effects of drugs on cognition, mood and behaviour (ie their psychoactive properties)
how can drugs have psychoactive properties?
drugs can only have psychoactive properties if they interact with existing endogenous neurochemical processes in the brain
what are the 2 types of psychopharmacological research?
- drugs can be used as ‘probes’ to study functions of endogenous neurotransmitter systems (NTs)
- investigation of drug effects ca also lead to development of treatments for medical/psychological conditions (Alzheimers, skits,depression ect)
what are the two themes?
research is difficult
- evidence needs interpretating, critically
we only know what we happen to have found out so far
- methods aren’t perfect, and many discoveries come about by chance
methodology for studying drug effects
as with most science, we need to compare with the effects in a control condition
what is a confound?
a confound is a potential alternative cause of what appears to be a drug effect
what are some examples of how confounds can be controlled for?
natural recovery
- control by: comparison with no-treatment group
expectation of drug effect
- control by: comparison with placebo condition (eg, sugar pill) and ensure “blinding” conditions
expectation can still occur with placebo controls if side-effects (or other drug effects) lead to correct guessing of participants condition (“unbinding”)
-control by: comparison with an active placebo condition (eg., another drug with similar noticeable effects)
what are the types of drug study
- randomised controlled trials- RCTs
- open-label trials
- “blinding” of conditions
- between-subjects design
- within-subjects
randomised controlled trials
these trials involve a control condition (eg placebo, but could be eg current best treatment) and random assignment of participants to groups
open-label trials
studies without blinding are referred to as being open-label. (there may still be a comparison with a control group eg placebo)
“blinding” of conditions
- blind= participant unaware of group assignment
- double blind= participant and researcher unaware of group assignment
= “unblinding” can occur when effects are detectable
between subjects design
= the comparison is between participants: drug group versus control group
within subjects designs:
= the comparison is between conditions for the same participants: drug condition when receiving drug versus control condition when receiving eg placebo
= for instance, a crossover design (eg., “AB/BA” : drug-then-control / control-then-drug. A “washout period” may occur between treatments.)
measures of drug effects include:
- changes in subjective experience (‘phenomenology’) and mood (self-report alertness, happiness, anxiety ect)
- changes in physiological activity (fMRI, EEG, ect)
- changes in task performance (simple and choice RT tasks, vigilance tasks, memory, problem solving, ect)
- changes in behaviour (social co-operation, aggression, hyperactivity, ect)
- NB subjective measures (eg ratings by self or researcher) can be susceptible to bias or expectancy- hence double-blind technique
neurocognitive models
- aim to explain the relationships between specific neurotransmitters systems, cognitive processes and subjective experiences
- the model could be of a type of drug effect (stimulant, edative, psychedelic, ect)
- or it could be of a neuropsychiatric conditions (adhd, depression, skits, ect)
what are 3 basic neurophysiological processes?
- neurons and synapses
- neurotransmitters and receptors
- agonistic and antagonistic effects of drugs
the neuron (nerve cell) and synapse
- dendrites receive chemical signals (neurotransmitters, NTs) from other neurons
- the cell body (soma) includes the nucleus, which controls cells activity
- the axon allows an electrical signal (action potential) to travel to axon terminal
- enzymes control synthesis of neurotransmitters, which are stored in vesicles and released from the axon terminal
- the signal is transmitted between neurons at the synapse
generation of action potential
- multiple excitatory and inhibitory signals (‘post- synaptic potentials’; PSPs) are integrated (combined) to determine whether an action potential is generated
- axon hillock: action potentials are triggered here if sufficient depolarisation (+relative to -)
- excitatory signals increase likelihood of receiving neuron producing action potential
- inhibitory signals decrease likelihood of receiving neuron producing action potential
endogenous processes involving neurotransmitters (NTs)
1) synthesised by enzymes and packaged in vesicles
2) released then bind with postsynaptic receptors
3) deactivated presynaptic reuptake or broken down by enzymes
effects of (NTs) at the post- synaptic cell
- 3-D shape of NT molecule has to fit receptor (like a key in a lock) to be able to produce an effect
- NTs influence the opening and closing of post-synaptic ion channels. this allows electrically charged ions to move in or out of the post-synaptic cell, making it more or less likely to ‘fire’ (produce an action potential)
- some NTs have less direct effects eg modulating the effect of other NTs on ion channels, or leading to other synaptic changes (eg for learning)
- the effect of a NT depends on receptor type. NTs therefore have different effects at different receptors
NT deactivation
- NT detaches from receptor and is then:
- transported back into the presynaptic neuron (reuptake)
or
-broken down by enzymes in the synaptic cleft (products of enzymatic breakdown may then be recycled)
how drugs work
- psychoactive drugs interact with NT systems
- drugs can influence NT synthesis, storage, release, receptor interactions, and/or deactivation
- drugs can have agonistic effects, where they mimic or enhance the effects of a NT
- drugs can have antagonistic effects, where they block or reduce the effects of a NT
some ways in which drugs interfere with endogenous processes
1) synthesised by enzymes and packaged in vesicles
2) released then bind with postsynaptic receptors
3) deactivated: presynaptic reuptake or broken down by enzymes
what are the two major neurotransmitters
glutamate and GABA work in opposition to each other to maintain the right balance between inhibition and excitation. both are found throughout the brain
- glutamate (glutamic acid) is the main excitatory NT, released by 50% of neurons. it is a precursor for GABA
- GABA (gamma-amino-butyric) is the main inhibitory NT, released by 40% of neurons. it is synthesised from glutamate
what are a few examples of GABA agonists
- benzodiazepines (BZDs), barbiturates and alcohol
what do these drugs do?
enhance the inhibitory effects of GABA and are:
- anxiolytic (reduces anxiety)
- sedative (reduce arousal/ increase relaxation)
- hypnotic (promotes sleep)
BZDs
(diazepam, temazepam, lorazepam, ect) are commonly prescribed for anxiety and are also used as pre-anaesthetic relaxants in surgery
barbiturates
are more potent GABA agonits- mainly used as general anaesthetics, to induce coma (eg after brain injury) and to treat epilepsy
what are a couple examples of GABA antagonists?
flumazenil and picrotoxin
flumazenil
blocks BZD site on GABA receptor; reverses BZD sedation (eg after medical operation); antidote for BZD overdose
picrotoxin
stimulant (increases arousal); convulsant (induces epileptic seizures at high doses); antidote for barbiturate overdose
glutamate agonists and antagonists
- glutamate agonists (eg ibotenic acid, found in poisonous mushrooms) are excitoxic- ie can kill nerve cells through over excitation
- ketamine= NMDA receptor antagonist; blocks excitatory effects of glutamate, used medically as sedative and anaesthetic
- NB glutamate has various receptor sub-types. the NMDA receptor (named after N-methyl-D-aspartate, an agonist for this receptor):
- is important in initiating the long-term synaptic changes necessary for learning and memory
- is also implicated in drug addiction, skits and epilepsy
