Dopamine, Glutamate, and Drug Use Flashcards
How do D2 receptors play a role in addiction issues? what does the evidence show?
- in an experiment participants got injected with radiactively labeled drug which binds to doapmine receptors
the experiment told us that in normal brains theres more activation of d2 receptors when given alcohol, calories, and cocaine
people who are dependent have less d2 receptors.. the reason for why this is the case is unknown
What does the number of dopamine receptors tell us about drug taking behaviours?
in an experiment volunteers where given ritalin and asked if it was pleasant or not
the people who found it unpleasant had less dopamine 2 receptors than people who found it pleasant
what does the study of primates in social hierarchy tell us about d2 receptors?
in primates, the alpha males have more d2 receptors than the beta males
the beta males also got addicted quicker than the alpha male did
the higher on the social standing you are, the less d2 receptors
so what do dopamine receptor levels tell us about addiction? what is the link?
addiction is correlated with lower dopamine receptor levels
brain studies have shown that chronic drug use and low d2 dopamine receptors in the striatum go hand in hand
What are the two types of dopamine receptors?
d1 receptors and d2 receptors
what is the difference between the d1 type receptors and d2 type receptors?
D1 type –> Gs coupled, which means it stimulates adenylyl cyclase, which increases cAMP levels and activates kinases
D2 type –> Gi/Go coupled, which inhibits adenylyl cyclrase, inhibits calcium channels, activates potassium channels and hyperpolarizes membrane
- D1 is on the post synaptic receptor only
- D2 is on the presynaptic autoreceptor (to clean up the NT’s in the cleft) and postsynaptic receptor
- D1 has an excitatory effect on NT’s
- D2 has an inhibitory effect on NTs
- D1 is involved in pathways associated with rewards
- D2 is involved in pathways associated with aversion
- D1 has low affinity for dopamine (active only at high concentration of dopamine)
- D2 has a high affinity for dopamine (1000X higher) and is activated at lower and even tonic levels of dopamine
overall D1 is activated during phasic (acute) release of dopamine and D2 is activated during tonic release of dopamine
what is the role of the presynaptic d2 receptors in addiction?
if you eliminate it, it alteres animals response to cocaine
human imaging studies show that people with low d2 receptors perceive a greater pleasureable experience from drugs
animals also displayed hypoerlocomotion without drugs and enhanced motivation for food reward and were supersensitive to cocaine effects
the reason for this is that the absence of d2 autoreceptors on the presynaptic neurons means no negative feedback to inhibit dopamine release
the dopamine wont get recycled back up and will stay in the cleft longer which means = more sensitivity, more locomotion
how do activating d2 receptors inhibit the neuron (3)?
- increases activity of potassium channel and decreases the activity of voltage gated calcium channel which leads to hyperpolarization of membrane
- increases numbers and activity of DAT (dopamine transporter) which vaccumes dopamine out of the synaptic cleft so it wont bind to the receptors
- decreases dopamine synthesis by inhibiting tyrosine hydroxylase (TH) enzyme… this is done by inhibiting adenylyl cylcase in the very begining causing less cAMP and less PKA and because theres nothing to phosphorylate TH, then it cant be made and therefore cant make dopamine
what happened when d2 autoreceptors genes were knocked out in mice?
they became more sensitive to cocaine
how do presynaptic receptors control the release of other neurotransmitters in the cortex?
majority of the d2 receptors arent on dopamine releasing neurons… theres evidence that they control glutamate as well
in the orbitofrontal cortex (part of PFC) and part of amygdala, communicate with striatal (nucleus accumbens and VTA) by releasing glutamate
dopamine may influence how these other brain areas influence the excitability of the striatum
what is the firing rate of dopamine neurons in the midbrain in a non-stimulated animal?
low frequency of 1-5/sec which is the basal or tone stimulation
what is the firing rate of dopamine neurons in the midbrain when animal is trained to self administer drugs or when a cue is trained to appear before a drug and the animal hears the cue?
then dopamine neurons will fire more at more than 20/sec
what were three experiments done on primates to show strength of dopamine signaling with an expectation of a reward?
- first experiment showed that dopamine response is linked to magnitude of the reward that is expected.. the higher the expectation of the reward the more dopamine is released. For example, showing primates pictures of symbols which represent different degrees of reward amount. The one that was associated with the most reward had the most dopamine increase vs. the one that was associated with no reward. There was no reward actually given in this experiment.
- Second experiment showed that dopamine neuron activity can increase or decrease once reward is received depending on their expectations. –> animals were shown an image that corresponded with an amount of sugar (as a reward) that they received. When monkeys were shown the ‘medium sugar’ reward and got no sugar or less sugar, their reward pathways temporarily shut down. But when shown the ‘medium sugar’ symbol and given more sugar than that, there was more activity than baseline for dopamine release.
- Third experiment showed that when monkeys were given two possible types of rewards (either small or medium) and either medium or large, their reward pathways lit up differently. When shown a symbol and expecting to get small or medium reward, their neurons shut down when they get a small reward instead of the medium, but when they get the medium reward their firing increases alot. In the medium to large symbol rewards, when monkey was shown a medium symbol their pathways shut down temporarily compared to when they got the higher reward. This tells us that depending on the expectation of the reward due to the symbol, a medium dose either increases firing rate or decreases firing rate
what does the anticipation of a reward tell us about doapmine release?
dopamine is not merely involved in reward, but also anticipation and comparison on a reward received to what was expected
what is a pre-reward dopamine release?
due to learned behaviour, cues, and expectations… cause more dopamine release
