Affective Neuroscience Model of Drug Effects (Lecture 4) Flashcards
psychoactive drugs definition
- natural receptor ligands and modulators (alter thoughts, feelings and behaviour)
- must cross the BBB
- processes that map on well to the brain and its neural hardware –> serve as natural ligands
natural efficacy of cocaine confirmed by carbon-11 labelling
- cocaine was labeled with C11 to track the distribution of and pharmacokinetics
- it measure cocaine phramacokinetics, relationship to behaviour AND was a sensitive radio tracer for DAT
- near perfect precision for DAT
evolutionary accounts of drugs in the ecosystem and the adaptive advantage to drug bearing plants
honey bees and tree shrews
- honey ferments to produce ethyl alcohol
- tree shrews consume this
animals consume plants –> they are efficient propagators of seeds of plants that want to spread –> working together
- when an animal eats coca it gets into the blood stream and BBB in trace levels
- the animal has an experience and encodes the plant as one that creates the experience –> acquires salience
- now they are more likely to eat that plant –> built in reinforcement at trace levels
what is the role of emotions and motivation in adaptive behaviour?
- emotions and sensations are effective signals for self regulation –> gives us the information we need to act in ways that are adaptive
emotions label a stimulus (+/-)
motivations translate them to corresponding behaviour
+ = approach stimulus
- = avoid stimulus)
role of consciousness in adaptive behaviour (Panksepp 1998)
- conciseness MEDIATES between neural events and adaptive behaviour when the drug enters the target site
the symphony and the soloist drugs effects
- drugs target and amplify natural signals
- symphony: when an animal eats a coca leaf they get pleasure but also energy because it is a stimulant that lets them forage for more
- soloist: the extracted drug stands out when selectively enhanced
patterns of drug use
- spontaneous/incidental
- recreational/intentional (consuming alcohol - recreational, ingesting coca leaves as a tool for more energy for labour - intentional)
- instrumental/goal oriented
what distinguishes drugs in nature and engineered drugs?
kinetics
- routes of administration
- natural drugs (ex. coca leaves) were ingested
- now we can administer them in different ways
- smoked cocaine gives more of a high than IV which gives more than snorted
potency
- the refinement of natural elements make the drug stronger (grinding into a powder and refining)
compensatory responses
- engineered drugs hit the target in a profound way which leads to compensatory responses for the disruption to maintain homeostasis such as down regulation of receptors
- these are critical to addiction
Panksepp’s 7 critical brain systems that guide adaptive behaviour
- these engage pain and motivation
- they modulate the stimulus they encounter and the following behaviour
seeking
rage
fear
lust
care
panic
play
Seeking
- basic emotional system
- key NT
- drug
basic emotional system
- positive motivation
- expectancy system
- finding food, water, exploration
key NT
- DA+, glu+, opioids+, neurotensin+, orexin+
drug: cocain
- indirect DA agonist
Rage
- basic emotional system
- key NT
- drug
- anger, negatively valence (unpleasant)
NT: substance P+, Ach+, Glu+
drug: modafinil - used to treat narcolepsy
- glu agonist
- associated with unpredictable rage
Fear
- basic emotional system
- key NT
- drug
anxiety
NT: glu+, CCK, DBI, CRF, NPY, alpha-MSH
drug: CCK, pentagastrin
- creates anxiety state
lust
- basic emotional system
- key NT
- drug
sexuality
- important for reproduction
NT: steroids (gonadal hormones)+, vassopressin+, oxytoxin+, LH-RH, CCK
drug: MDMA
- oxytocin associated with incredible closeness
care
- basic emotional system
- key NT
- drug
nurturance - no imminent fear of death
NT: oxytocin+, prolactin+, DA+, opioids+/-
drug: opioid
- state of care - at dose that does not put them to sleep
panic
- basic emotional system
- key NT
- drug
separartion
- flip side of care - extreme fear of death
NT: all are opposing, opioids-, oxytocin-, prolactin-, CRF-, glu+
drug: yohimbine
- noradrenergic
- knocks out opioids
- alpha2 blocker
- blocks feedback to create NE burst
play
- basic emotional system
- key NT
- drug
joy - critical for socializing
NT: opioids+/-, glu+, ach+, cannabinoids
drugs: cannabis, morphine
PAG
- where the MOR is most abundant
- interspace between forebrain and brainstem
- ingrates physiological and emotional responses that are essential to survival
- projections from the PFC to the CeA to the PAG to the brainstem mediate active and passive coping responses to facilitate survival
PAG and psychiatric disorders
- it integrates negative emotions with autonomic, neuroendocrine and immune systems to facilitate responses to threats –> same regions as in anger/fight, fear/panic, depression/shutdown, pain and predatory behaviours in response to challenging situations/threats
- when activated pathologically it can result in symptoms of psychiatric disorders
- capacity to respond is lost and we see psychiatric symptoms (commonly depression)
Affective neuroscience perspective on depression and addiction medication
depression - enduring grief
- effects of chronic stress
- SSRIs and SNRIs have modest effects (33%) and a wide variability of response
addiction - compulsive seeking
- medications for nicotine and alcohol dependence but only 33% more effective than placebo
- however, opioid replacement therapy with methadone works well
affective neuroscience account of depression - effects of
- basis of depression revolves around the process in which separation distress is normally shut down - possibly primary effects in kappa opioids on VTA output
emotional pain/distress –> intolerance –> need to escape + despair –> suicide
the effects of buprenorphine, ketamine and naltrexone on suicidality
buprenorphine
- decreased suicidality of people with depression + PTSD
- KOR likely mediates the antidepressant and some anxiolytic effects of buprenorphine
- it is an partial u agonist and k antagonist
ketamine
- acts rapidly to reduce state of depression and reduce suicidal state
- NMDA antagonist which also has effects on the u opioid receptor to restore opioid signal
- naltrexone blocks the antisuicidal affects of ketamine
- it is an opioid antagonist that caused an increase in suicidal symptoms when compared to placebo after they were lowered with ketamine
affective neuroscience account of addiction
- addiction is a substitute for the attainment of a secure love object
- residual effect of experience between mother and child carries over as risk for addiction
- positive child bearing and childhood experience it provides the neurochemical foundations and model for how to bond with others
- when it is disturbed a person can be depressed or try to replace it –> seeking temporary relief from missing care
effects of naltrexone and nalmefene on addiction
Naltrexone
- naltrexone blocks craving for alcohol, gambling and rewarding effects of nicotine and amphetamine
- carving to belong to a love object is dam[ended down the same way as craving for drugs (craving activates mu –> blocking mu blocks craving)
- the mu opioid receptor is important in the pleasure people derive from addiction
nalmefene
- even stronger KOR antagonist effects - may be more effective for craving
- by blocking kappa you block the unpleasant state of craving
what common motivation does suicide and craving alcohol have?
desire to escape emotional pain
- same effects reduce suicidality and alcohol craving
- what is being treated is the desire to escape emotional pain
- when we treat this the levels of suicidality and alcohol craving get better which supports the validity of this model
