L2 - INTRODUCTION TO THE NEUROBIOLOGY OF ADDICTIVE DRUGS Flashcards
What are the principal output(s)/input(s) of the mesocorticolimbic dopamine pathway?
Output: VTA
Inputs: NAcc (also projecting back to VTA) and PFC
What are the two common ways drugs of abuse stimulate dopamine transmission?
- Activating (or disinhibiting) VTA DA cell firing.
- Increasing the amount of DA released at synaptic terminals.
What drugs from the list below are stimulating dopamine transmission by activating (or disinhibiting) VTA DA cell firing? By increasing the amount of DA released at synaptic terminals?
Cocaine, Heroin, Morphine, Amphetamine, Nicotine, Phencyclidine, Alcohol, Methamphetamine.
By activating (or disinhibiting) VTA DA cell firing:
Heroin
Morphine
Alcohol
Nicotine
By increasing the amount of DA released at synaptic terminals:
Cocaine
Amphetamine
Methamphetamine
Phencyclidine
Generally explain how the synaptic DA transmission occurs.
- Phenylalanine is converted to dopamine
- DA sequestered in vesicles (picked up by vesicle transporter)
- Opening of voltage-gated Ca++ channels
- Vesicles migrating to membrane for fusing
- DA molecules are liberated in the synaptic cleft and bind
D1 receptors
D2 receptors - Postsynaptic potential is created (can be either IPSP or EPSP, depending on receptor)DA is re-uptaken by protein transporters (DAT)
- MAO breaks down dopamine → deamination → DOPAC (secreted in the extracellular space) → HVACOMT converts unbound DA to 3-MT (COMT is not present at the same levels in every area of the brain)
Describe the neurobiological effects of amphetamine on the synaptic transmission of dopamine.
Amphetamine consequences on DA trans.
- Displaces DA in vesicles (competitive)
- DAT is reversed bc. of higher DA intracellular concentration → synaptic cleft is filled with more DA
- MAO inhibition → accumulation of DA
Describe the neurobiological effects of cocaine on the synaptic transmission of dopamine.
Blocks DAT reuptake.
Describe the neurobiological effects of opiates on the synaptic transmission of dopamine.
Inhibits GABA neurons (in VTA and NAcc) = disinhibitation = increased DA release from axon terminal
True or false: some neurons of the NAcc project back on the dopaminergic neurons of the VTA.
True.
How are the dopaminergic neurons of the VTA regulated?
By (1) GABA neurons from VTA (interneuron) and (2) GABA neurons from NAcc (forming a negative feedback loop)
To what kind of receptor does bind heroin and morphine on the GABAergic neurons of the mesocorticolimbic dopamine pathway?
The μ-opioid receptors.
What phenomenon would be observed after repeated, closely spaced administration of an addictive drug concerning its effects?
Tolerance.
After a drug-free period, what phenomenon can be observed subsequently to drug administration?
Sensitization.
How long does last sensitization to an addictive drug?
Months, years, permanently perhaps.
Liking, wanting and learning are interdependant processes elicited in response to what?
Rewards.
How does one learn from rewards?
Reward-associated cues acquire PREDICTIVE and INCENTIVE properties.
How are the predictive and incentive properties of a reward differentiating?
The incentive properties drive the compulsion to seek the reward while the predictive properties stress the reward availability.
What is the role of the motive circuit?
Assigning predictive and incentive properties to reward-associated cues.
Regarding incentive and predictive properties of a reward, what can a Pavlovian Conditioned Approach (PCA) be used for?
Dissociating incentive and predictive properties of a reward, which are normally strongly associated.
What does PCA reveal concerning individual differences in response to reward cues?
Dissociating the predictive and incentive motivational properties of reward cues shows that some individuals are sign trackers (STs) and others goal trackers (GTs).
How do sign trackers and goal trackers differ?
The conditioned stimuli (CS) associated to the reward has predictive value for both STs and GTs. However, only the STs show that the CS gained incentive salience (work will be done to earn CS presentations).
In regards to DA levels in the NAcc, how are STs and GTs differentiating?
STs show a high DA response to CS, but no DA response to reward. GTs show a moderate DA response to CS, but a higher DA response to reward.
What is neurobiologically necessary for processing the emergent incentive salience of reward cues?
Release of DA NAcc.
Concerning behavior in relation to reward cues, what would be the consequence of a DA receptor blockade in NAcc?
Impairing the acquisition and expression of sign-tracking behavior (GT behavior would be sensibly the same).
DA receptor blockade in NAcc impairs ST behavior but not GT behavior. Provide a hypothesis to this observation.
Since the receptor blockade acts probably on one specific type of receptor, it is possible that the medium spiny neurons of the NAcc that are either D1 or D2-prominent correspond to a ST or GT behavioural profile.
