lecture 16 LOs Flashcards
reinstatement paradigm for relapse in animal models
- train rats to administer drug (cues can be presented with drug infusion)
- take rat through extinction (lever press no longer delivers drug or cue, rat stops pressing)
- on test day no drug is provided but reinstatement of lever pressing can be induced by a drug prime, or a stressor, or a drug associated cue
what can a drug taste, drug related cue, or stress do to lever pressing
it can increase it in the absence of drug administration
what brain areas are the ability of the triggers (stressor, drug taste, drug associated cue) mediated by in the DA system
PFC, accumbens, amygdala
how do addictive drugs affect mesolimbic DA levels
dramatically increase the DA levels
DA doesnt mediate pleasure, but it does play a major role in wanting
what do drug induced increases in DA do to your brain
trick it into thinking that smth important is happening so it starts making associations with the environmental cues linked w drug taking
what does reward associated cues increasing DA release into the accumbens do
triggers the same behaviours that got you the rewards in the first place (aka drug seeking)
what can prolonged drug use do to the brain
induce a hyperactive (or sensitized) DA system
increased DA transmission can amplify the effects that drug-related cues exert over behaviour
what is the DA and addiction incentive sensitization hypothesis
cues associated with drug taking take control over behaviour
initial drug taking driven by pleasurable drug effects
over time tlerance develops to hedonic effects (you start to like the drug less)
however, effects on the DA system and the learning about drug related cues becomes sensitized
what happens to the associative memories between the drugs effect and their related cues in a hyperdopaminergic state
amplification
drug cues trigger more craving and then more drug taking, even if the effects of the drug aren’t as pleasurable
what is DA sensitization w repeated drug use
repeated drug use makes the DA system more responsive to drug related cues and stress
this results in changes in neural networks (rather than just DA neurons) that include the VTA, PFC, and the NAc
enhanced DA is thought to promote craving and drug seeking behaviours in response to triggers (like stress or drug related cues)
what would within system adaptations of neuroadaptations with repeated drug use result in
down regulation of reward circuitry (tolerance to pleasurabe affects of drugs)
what would between system adaptations and gradual recruitment of the anti reward system do in neuroadaptations with repeated drug use
stress and adversion related circuits that include NE, peptide transmitters, and dynorphin, the central nuecles of the amygdala and the NAc
what is physical withdrawal
can contribute to drug cravings and maintenance of addiction, it cannot explain all aspects of the behaviour though
initially what circuit do drugs activate
reward circuit promoting drugs positive reinforcing effects
after repeated drug use what happens to drugs ability to activate the reward circuitry
drugs become less effective at it
as drugs become less effective at activating the reward circuitry, what else happens
the acitvation of the anti-reward system increases, involving the release of NE, CRF, and dynorphin
what are the two major functions of the anti-reward system
mediates some of the aversive effects of stress
puts a limit on reward functions
when is the anti-reward system activated
during withdrawal
plays a major role in the aversive effects and the negative emotional states (ex depressed mood)
what does the anti-reward and reward circuitry theory propose
that drug addiction is driven by motivation to alleviate negative emotional states associated w withdrawal
what happens with the positive and negative effects of drugs w repeated use
positive effects get shorter and weaker
negative effects get larger and last longer
what type of abnormalities have been found in drug addicts
PFC structural and functional abnormalities
what do MRI studies show about the grey matter volume in drug users
reduced grey matter, sometimes even after long periods of abstinence
we don’t know if this is a predisposition to drug addiction or if its caused by addiction or even both
what does imapired PFC function in addicts result in
impaired flexibility and increased impulsivity
may also contribute to intrusive thoughts and cravings of drug taking
what happens to the D2 receptors in addicts
they have fewer D2 receptors
are proposed to serve as a brake function on certain actions
does alcohol enter the brain
yes
what do lower doses of alcohol do
disinhibition, euphoria, relaxation
what do higher doses of alcohol do
slurred speech, impaired motor coordination and memory
how does alochol effect neural activity at higher and lower doses
lower: preferentially suppresses inhibitory interneurons and has stimulant (dishinhibitory) like effects
higher: causes broad suppression of cortical pyramidal neuron activity
how does alocohol diffuse in the body
across membraines of GI tract into the blood
greater alcohol concentration consumer results in more rapid diffusion
what is alcohol metabolized by
alcohol dehydrogenase (in the liver and gastric fluid)
