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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
Q

Appetitive learning

A

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

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26
Q

Other than dopamine what else is likely to contribute to drug induced reward and addiction

A

Use-dependent changes in other NT, intracellular signaling pathways, transcription factors

27
Q

A patter of chronic, escalating, and compulsive drug use despite adverse consequences.

A

Addiction

28
Q

Stages of addiction development

A
  • 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
Q

What happens to the VTA, nucleus accumbens, and prefrontal cortex during drug abuse

A

Structural and neurophysiological plasticity

30
Q

Drug induced neurophysiological plasticity include schanges in

A

Dopamine and other NT receptors, synaptic re-uptake transporters, intracellular signaling pathways downstream to metabotropic NT receptors, transcription factors

31
Q

Drug induces structural plasticity

A

Synapse number and density, dendritic arbor, axon terminals

32
Q

Drug addiction in different people

A

Significant individual variability in whether initial drug use leads to addiction
-risk factors: trauma, physical/sexual abuse, MDD, anxiety

33
Q

Blocks pre synaptic dopamine re-uptake transporter

A

Cocaine

34
Q

Blocks pre-synaptic dopamine re-uptake transporter and can also cause reversal of flow of dopamine through re-uptake transporter back into synapse

A

Methamphetamine

Amps synaptic signaling

35
Q

Amphetamine psychosis: manic, delusional, paranoia

A

Methampehtamine and MDMA (ecstasy)

36
Q

What can the use of methamphetamine and MDMA cause

A

Potential neurotoxicity

37
Q

What is enkephalin synthesized from

A

Gene

38
Q

What is dynorphin synthesized from

A

A gene

39
Q

What is B-endorphin synthesized from

A

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
Q

Membrane metabotropic receptors for endogenous opioids

A

Mu
Kappa
Delta

41
Q

Mu receptors

A

Bind enkephalin and opioids drugs

42
Q

Kappa receptors

A

Bind dynorphoin

43
Q

Delta receptors

A

Bind enkephalin

44
Q

Opioids receptor functions

A

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
Q

Neurobiological basis of addiction

A

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
Q

Psychoactive substance in marijuana

A

THC

47
Q

Receptors of endogenous canabinoids

A

Anandamide

2-AG

48
Q

What are anandamide and 2-AG synthesized from

A

Phospholipids

49
Q

What do anandamide and 2-AG act as

A

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
Q

Where is CB1

A

Widely in the brain

51
Q

Where is CB2

A

Mainly in hypothalamus

52
Q

Prefrontal cortex and cannabinoids and THC

A

Act similarly to local inhibitory internuerons, so excess activation of CB1 can slow or impair cognitive function

53
Q

Reward systems and marijuana

A

Enhances mesolimbic dopamine system activity

54
Q

Hypothalamus and marijuana

A

Activates the orexic systems and suppresses the HPA axis (cortisol) by inhibiting activity of CRH releasing neurons in hypothalamic paraventricular nucleus

55
Q

Hallucinogens and marijuana

A

Proabably indirect effect of inhibiting ongoing sensory info processing in favor of spontaneous neuronal activity in sensory cortex

56
Q

Potential for addiction: marijuana

A

Controversial

57
Q

PCP and ketamine effects

A

Euphoric, hallucinogenic, can lead to psychotic symptoms

58
Q

Neural mechanism of PCP and ketamine

A
  • reward system activation: mesolimbic dopamine system

- hallucinogenic properties: blockade of NMDA-type glutamate receptors

59
Q

When does ketamine act like PCP

A

At low levels

60
Q

What is ketamine normally

A

General anesthetic

61
Q

Mechanism of alcohol (and nicotine)

A

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
Q

What neurons does ethanol activate directly (and nicotine)

A

VTA

63
Q

What should primary care provider look at when looking at drug use

A

Look beyond drugs use itself to the underlying drivers

64
Q

Major drivers of addiction besides activation of reward system

A
  • 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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