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Neuro Block 8 > Motivational Systems, Drugs, And Addiction > Flashcards

Motivational Systems, Drugs, And Addiction Flashcards

1
Q

What are the two main dopamine systems

A

Mesolimbic system

Nigrostriatal system

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2
Q

What is the main dopamine projection system

A

Mesolimbic system

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3
Q

Motivational loop and motor loops

A

Nigrostriatal

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4
Q

What does the nigrostriatal system consist of

A

From SN to caudate N and putamen

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5
Q

What nucleus participates in the motivational and motor loops

A

Caudate

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6
Q

What does the mesolimbic system consist of

A

From tegmental area to prefrontal cortex, nucleus accumbens (ventral striatum), amygdala, hippocampus, other limbic regions

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7
Q

What is the mesolimbic system important for

A

Selective attention (prefrontal), natural reward seeking, and involved in drug addiction

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8
Q

Where is the nucleus accumbens positioned

A

At anterior end of striatum and in a ventral position

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9
Q

What two structures does the nucleus accumbens continue with

A

Caudate and putamen

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10
Q

Anterior commisure and the ventral pallidum

A

Portion of striatum lying ventral to anterior commissure crossing

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11
Q

What loops are the nigrostriatal DA system involved with

A

Motor loops and cognitive loops

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12
Q

What loops are the mesolimbic DA system involved with

A

Motivational (emotive) loop

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13
Q

What striatal region is involved in the motivational loop

A

Ventral striatum

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14
Q

What striatal region is involved in the motor loop

A

Putamen and caudate

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15
Q

What striatal region is involved with the cognitive loop

A

Caudate nucleus

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16
Q

What are dopamine neurons activated by

A

Emotionally positive (and negative) stimuli and cues that indicate these rewards are available

  • food/nutrients
  • socal: fam/friends/mates
  • sexual arousal/activity
  • music
  • money
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17
Q

Dopamine release in target regions

A

Nucleus accumbens

-critical for normal behavior and reward seeking

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18
Q

Impairment in dopamine release can lead to reduction in

A
  • eating, other rewarding activities, spontaneous physical activity, normall mediated by dopamine regulation of: accumbens, orbital cortex, amygdala, hypothalamus
  • attention and working memory (prefrontal)
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19
Q

What part of the mesolimbic system is strongly activated by various drugs

A

Ventral tegmentum

Nucleus accumbens

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20
Q

What are the drugs that affect the nucleus accumbens

A
  • amphetamine
  • cocaine
  • opiates
  • THC
  • phencyclidine
  • ketamine
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21
Q

What drugs affect the ventral tegmental area

A
  • opiates
  • ethanol
  • barbiturates
  • benzodiazepines
  • nicotine
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22
Q

How do they test to see what parts of the brain are affected by certain drugs

A

They directly stimulate a part of the brain and see if rats will press lever for more.

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23
Q

Activation of the mesolimbic dopamine system following drug use

A

Serves to reinforce the emotive or motivational loop circuits, which reinforces drug seeking and drug use. Drugs usually induce greater activation of the mesolimbic dopamine system than natural rewards

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24
Q

Activation of the mesolimbic dopamine system following drug use, including activation of the amygdala and hippocampus

A

Also serves to add a strongly positive emotional value to any sensory cues associated with drug use or drug availability

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25
Appetitive learning
Sensory cues that were previously emotionally neutral sensory stimuli gain a strongly positive emotional value. These stimuli alone gain the ability to activate the mesolimbic dopamine system and this stimulus induced is believed to be involved in drug-craving
26
Other than dopamine what else is likely to contribute to drug induced reward and addiction
Use-dependent changes in other NT, intracellular signaling pathways, transcription factors
27
A patter of chronic, escalating, and compulsive drug use despite adverse consequences.
Addiction
28
Stages of addiction development
- repeated drug use escalates in frequency or dose or both - tolerance: higher doses needed - psychological dependence: continued use required to maintain normal function - dysphoria and withdrawal: periods of non use lead to emotional distress or depressed moods - relapse: triggered by exposure to drug or associated cues
29
What happens to the VTA, nucleus accumbens, and prefrontal cortex during drug abuse
Structural and neurophysiological plasticity
30
Drug induced neurophysiological plasticity include schanges in
Dopamine and other NT receptors, synaptic re-uptake transporters, intracellular signaling pathways downstream to metabotropic NT receptors, transcription factors
31
Drug induces structural plasticity
Synapse number and density, dendritic arbor, axon terminals
32
Drug addiction in different people
Significant individual variability in whether initial drug use leads to addiction -risk factors: trauma, physical/sexual abuse, MDD, anxiety
33
Blocks pre synaptic dopamine re-uptake transporter
Cocaine
34
Blocks pre-synaptic dopamine re-uptake transporter and can also cause reversal of flow of dopamine through re-uptake transporter back into synapse
Methamphetamine Amps synaptic signaling
35
Amphetamine psychosis: manic, delusional, paranoia
Methampehtamine and MDMA (ecstasy)
36
What can the use of methamphetamine and MDMA cause
Potential neurotoxicity
37
What is enkephalin synthesized from
Gene
38
What is dynorphin synthesized from
A gene
39
What is B-endorphin synthesized from
A post translational cleavage product of the pituitary hormone PMC, which is also cleaved to produce ACTH, which stimulates adreanl cortex to release cortisol
40
Membrane metabotropic receptors for endogenous opioids
Mu Kappa Delta
41
Mu receptors
Bind enkephalin and opioids drugs
42
Kappa receptors
Bind dynorphoin
43
Delta receptors
Bind enkephalin
44
Opioids receptor functions
Widely distributed in the brain, so diverse functions - emotional response to pain - appetite and craving salt, sweets, food - playability of food - reward seeking of various kinds - mood
45
Neurobiological basis of addiction
Possible contributing factors - rewarding activities and stimuli increase endogenous opiates - synthesized and released as NT by dopamine neurons - opiate drugs can become mroe rewarding than natural stimuli - reduce anxiety or other negative emotions: learned self medication
46
Psychoactive substance in marijuana
THC
47
Receptors of endogenous canabinoids
Anandamide | 2-AG
48
What are anandamide and 2-AG synthesized from
Phospholipids
49
What do anandamide and 2-AG act as
Retrograde messengers: released from post synaptic sites, diffuse across synapse and bind to pre synaptic auto receptors to regulate pre synaptic NT release, mainly glutamate and GABA release -two proteins coupled receptors: CB1 and CB2 generally inhibitory
50
Where is CB1
Widely in the brain
51
Where is CB2
Mainly in hypothalamus
52
Prefrontal cortex and cannabinoids and THC
Act similarly to local inhibitory internuerons, so excess activation of CB1 can slow or impair cognitive function
53
Reward systems and marijuana
Enhances mesolimbic dopamine system activity
54
Hypothalamus and marijuana
Activates the orexic systems and suppresses the HPA axis (cortisol) by inhibiting activity of CRH releasing neurons in hypothalamic paraventricular nucleus
55
Hallucinogens and marijuana
Proabably indirect effect of inhibiting ongoing sensory info processing in favor of spontaneous neuronal activity in sensory cortex
56
Potential for addiction: marijuana
Controversial
57
PCP and ketamine effects
Euphoric, hallucinogenic, can lead to psychotic symptoms
58
Neural mechanism of PCP and ketamine
- reward system activation: mesolimbic dopamine system | - hallucinogenic properties: blockade of NMDA-type glutamate receptors
59
When does ketamine act like PCP
At low levels
60
What is ketamine normally
General anesthetic
61
Mechanism of alcohol (and nicotine)
Non specific inhibitory mechanisms via action at axons -specific sites of action currently under investigation: inhibition of glutamate and serotonin receptors, possibly other undiscovered specific mechanisms
62
What neurons does ethanol activate directly (and nicotine)
VTA
63
What should primary care provider look at when looking at drug use
Look beyond drugs use itself to the underlying drivers
64
Major drivers of addiction besides activation of reward system
- self medication of anxiety - self medication of other negative emotions - self medication of Dx or unDx mental health disorders

Neuro Block 8 (11 decks)

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