Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neurobiology -BIOL4370 > Lecture 7-Neuropharmacology of Addiction > Flashcards

Lecture 7-Neuropharmacology of Addiction Flashcards

1
Q

What is homeostasis?

A

It is the process of regulating the body’s internal environment to maintain stability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What key role does the hypothalamus play in homeostasis?

A

It regulates body temperature, thirst (fluid balance), and hunger (energy balance).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How does the brain detect and respond to deviations from homeostasis and what kinds of responses are triggered?

A

The periventricular zone of the hypothalamus detects deviations from the optimal range and triggers a coordinated multi-brain region response to restore balance
-This includes cognitive, behavioral, endocrinal, physiological, and hormonal responses.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the three types of hypothalamic responses?

A
  1. Humoral
    - Hypothalamic neurons stimulate or inhibit pituitary hormone release. For example, a hormone might trigger egg-laying behavior in turtles.
  2. Visceromotor:
    - Hypothalamic neurons adjust the autonomic nervous system (ANS) to control functions like respiration and blood vessel constriction.
  3. Somatic Motor:
    - The lateral hypothalamus induces motor behaviors, such as motivated actions to restore balance.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does the hypothalamus act as a “setpoint hub”?

A
  1. Integrates data from the forebrain, brainstem, and spinal cord.
  2. Compares sensory inputs (e.g., visceral and hormonal signals) and contextual inputs (e.g., amygdala, cortex) to biological setpoints.
  3. Activates appropriate responses (e.g., motor and hormonal systems) to maintain homeostasis.

Adjusts actions based on body feedback (e.g., adjusts heating responses if the body warms up after being cold).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does the hypothalamus do to regulate body weight?

A

It surveys hormone levels, detects changes, and initiates compensatory mechanisms to maintain body weight at a setpoint.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the body’s setpoint for weight, and how does the hypothalamus regulate it?

A

The setpoint is the body’s target weight that the hypothalamus maintains by adjusting hunger and metabolism.
- If weight drops (starvation), it increases hunger and slows metabolism.
- If weight rises (overfeeding), it decreases hunger and speeds up metabolism.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the role of the lateral hypothalamus (LH) in feeding behavior?

A

Cruical in regulating feeding behavior and triggers feeding when stimulated, even if the animal is satiated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How is feeding behavior initiated in the brain?

A

Reduced hormone levels are detected by neurons in the paraventricular nucleus (PVN), which then signal the lateral hypothalamus to start feeding behavior.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does the Ob gene code for, and what happens if it is knocked out?

A

The Ob gene codes for leptin, which binds to receptors in the brain’s lateral hypothalamus to signal fullness (satiety). If it is knocked out, the brain does not receive signals about fat reserves, causing the animal to overeat and become obese

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What was the parabiosis experiment, and what did it demonstrate?

A

It joined the circulatory systems of normal and ob/ob mice.
- Leptin from the normal mouse reduced obesity in the ob/ob mouse, proving leptin’s role in signaling fat reserves.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How is leptin produced, and how does it regulate body mass?

A
  • Produced by adipocytes (fat cells)
  • Acts on hypothalamic neurons to decrease appetite and increase energy expenditure, regulating body mass.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What did Friedman discover about leptin in 1994?

A
  • He isolated leptin showed that treating ob/ob mice with leptin reversed obesity and eating disorders by regulating appetite through hypothalamic neurons.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the characteristics of humans lacking leptin, and how does it affect their metabolism?

A

Humans without leptin experience intense food cravings, a slowed metabolism, and severe obesity, as their brain and body act as if they are always starving.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why is leptin supplementation not always effective in treating obesity?

A
  1. Decreased ability of leptin to cross the blood-brain barrier.
  2. Altered central nervous system response to hypothalamic activity (Even if leptin binds to receptors, the hypothalamus may not activate pathways to reduce appetite or boost energy use).
  3. Reduced expression of leptin receptors (makes it difficult for the brain to detect leptin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What did Hetherington and Ranson discover about the hypothalamus in rats?

A

Lesions in the lateral hypothalamus (LH) caused anorexia, while lesions in the ventromedial hypothalamus (VMH) led to overeating and obesity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the role of the ventromedial hypothalamus (VMH)?

A
  • The VMH regulates eating behavior (controls hunger and satiety) and coordinates the physical eating process (mechanics of eating and digestion)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What happens when leptin binds to receptors in the arcuate nucleus (AN) of the hypothalamus following a big meal?

A
  • Leptin binding in the AN triggers the release of
    αMSH (Alpha Melanocyte Stimulating Hormone) and CART (Cocaine and Amphetamine Regulated Transcript), neurotrasnmitters that suppress appetite and increase energy expenditure.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What changes are triggered by elevated αMSH and CART in the humoral response?

A

Increased secretion Thyroid stimulating hormone (TSH) and
Adrenocorticotropic hormone (ACTH), which act on the thyroid and adrenal glands to raise the metabolic rate of cells (makes cells work faster to burn more energy)
- This supports energy balance, preventing excessive fat storage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are αMSH and CART, and what is their primary function?

A

αMSH and CART are anorectic peptides that act as appetite suppressants by mimicking elevated leptin levels and diminishing feeding behavior.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How do αMSH and CART trigger the humoral response?

A

They activate neurons in the paraventricular nucleus (PVN), which controls the release of TSH and ACTH from the anterior pituitary to increase metabolism.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the difference between leptin and αMSH/CART in energy regulation?

A
  • Leptin is a hormone that acts as the “messenger” to tell the brain there is enough energy
  • αMSH and CART are neurotransmitters in the hypothalamus that act as “workers,” reducing appetite and increasing metabolism in response to leptin’s signal.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What responses do αMSH and CART trigger in the hypothalamus? (Summary)

A

They trigger the
1. Visceromotor response: Increasing sympathetic tone, metabolic rate, body temperature
2. Somatic Motor Response: Decreasing feeding behaviour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How can blocking αMSH and CART receptors benefit individuals undergoing chemotherapy?

A

Blocking αMSH and CART receptors can stimulate feeding by counteracting their appetite-suppressant effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does leptin affect feeding behavior via the hypothalamus?

A

Increased leptin activates αMSH and CART in the arcuate nucleus, which signals the PVN to inhibit feeding and increase energy expenditure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What happens when leptin levels decrease in the hypothalamus?

A
  • Low leptin activates alternative arcuate nucleus neurons.
  • These neurons produce Neuropeptide Y (NPY) and Agouti-related peptide (AgRP).
  • They stimulate melanin-concentrating peptide (MSH)-containing neurons in the lateral hypothalamus, promoting feeding behavior.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How do αMSH and AgRP function as antagonistic neurotransmitters in feeding regulation?

A

αMSH: Activates MC4 receptors to suppress feeding.

AgRP: Blocks MC4 receptors to stimulate feeding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the MC4 receptor, where is it located, and what is its role?

A

The MC4 receptor is a postsynaptic receptor located in the lateral hypothalamus
- Role: Inhibit feeding behavior when activated.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How do AgRP and NPY increase feeding behavior?

A

AgRP and NPY act together to inhibit MC4 receptors in the lateral hypothalamus, reducing the satiety signal and promoting feeding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

How do orexin and MCH cells regulate feeding behavior?

A

Orexin cells, found in the lateral hypothalamus
initiate feeding behavior by signaling hunger, while MCH cells maintain and prolong feeding, ensuring continued consumption.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the active ingredient in marijuana and what does it stimulate?

A

The active ingredient in marijuana is THC (D-tetrahydrocannabinol), which stimulates cannabinoid receptor-1 (CB1).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How does cannabinoid receptor-1 (CB1) receptor activation affect the hypothalamus?

A

CB1 receptor activation in the hypothalamus increases appetite (orexigenic effect) and enhances the sense of smell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How does CB1 activation impact inhibitory neurons in the olfactory bulb?

A

CB1 reduces excitatory input to inhibitory granule cells, making them less active and disinhibiting olfactory bulb neurons, This allows olfactory bulb neurons to become more active, which increases the sense of smell and increases feeding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How did stimulating a rat’s brain influence its behavior?

A

When rats were given brain stimulation in certain areas, they preferred the part of the box where the stimulation occurred, showing that the brain’s reward system motivates behavior.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What happens when animals can self-stimulate their brain with a lever, especially when electrodes are placed in the ventral tegmental area (VTA)?

A

They prioritize brain stimulation over basic needs like food and water, showing the strongest reward response and self-stimulating until exhaustion.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is the role of the ventral tegmental area (VTA) in motivation?

A

The VTA provides dopaminergic projections and stimulates areas like the lateral hypothalamus and forebrain regions to control goal-directed behavior.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Why did animals persist in self-stimulating their brain, even at the expense of basic needs?

A

This behavior occurred because self-stimulation of the brain appeared to provide a reward that reinforced the behavior.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How does blocking dopamine receptors (specifially D1 subtype) affect self-stimulation in rats?

A

Blocking dopamine receptors reduces self-stimulation behavior, indicating dopamine’s role in reinforcement.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is the mesocorticolimbic dopamine system, and where does it project?

A

It is a dopamine pathway where the VTA projects to regions like the nucleus accumbens and prefrontal cortex, influencing reward, decision-making, and goal-directed behavior.

40
Q

How are D1 receptor antagonists relevant in addiction treatment?

A

D1 receptor antagonists are used to reduce dopamine-driven reinforcement, helping manage addictive behaviors.

41
Q

Why were electrodes implanted in patients during Heath’s 1960s experiments?

A

The electrodes were implanted to study self-stimulation in patients with severe narcolepsy (involuntary deep sleep onset).

42
Q

What brain area did the first patient prefer to stimulate, and why is it significant?

A

The first patient preferred stimulating the septal area, which is significant because it receives dopamine projections from the VTA.

43
Q

What brain area did the second patient prefer to stimulate, and how did they describe the sensation?

A

The second patient preferred stimulating the medial thalamus and described the sensation as “feeling like about to recall a memory.”

44
Q

What happens when dopamine axons are destroyed in animals?

A

Animals still show a pleasurable response to food, such as licking their lips, but they lose the motivation to seek out the food.

45
Q

How does the role of dopamine in food-related behavior differ from the common belief about it?

A

While dopamine was once thought to be solely linked to pleasure or reward, it is more involved in the motivation to seek food, not just the enjoyment of eating.

46
Q

What did Wolfram Schultz’s initial experiment on dopamine signaling show?

A

The experiment showed that VTA neurons fired more when monkeys were given juice, even without the light-juice association.

47
Q

How did the light and juice pairing affect VTA neuron activity in Schultz’s experiment?

A

After several pairings of light and juice, the light alone started to trigger the reward, causing VTA neurons to fire in anticipation instead of just in response to the reward.

48
Q

What did the VTA neuron activity reveal when the juice was not given after the light?

A

When the juice was absent after the light, VTA neurons decreased firing, signaling a reward prediction error—indicating that the outcome was worse than expected.

49
Q

What role do VTA neurons play in reward processing according to Schultz’s findings?

A

VTA neurons signal both anticipation of rewards and prediction errors when the expected reward is not received, helping adjust future expectations.

50
Q

What is the setup for the self-stimulation experiment?

A

Electrodes are implanted in brain areas that activate dopaminergic pathways from the ventral tegmental area (VTA) to explore how certain drugs affect the brain’s reward system.

51
Q

How do cocaine and nicotine affect self-stimulation behavior and the rate of stimulation?

A
  • Increase the rate of electrical self-stimulation, with the animal pressing the lever more as the stimulation current frequency increases.
52
Q

What is the overall effect of cocaine and nicotine on the brain’s reward system?

A
  • These drugs lower the threshold for rewards, so animals feel the reward more easily and don’t need to press the lever as much.
  • Enhance the salience of rewards by increasing the sensitivity of the brain’s reward system, leading to more frequent self-stimulation overall
53
Q

What is the primary brain reward circuit and how does it function?

A

The primary reward circuit involves dopaminergic projections from the VTA to the NAc, where VTA projections release dopamine in response to reward-related stimuli.

54
Q

What role does the amygdala play in drug use?

A

The amygdala forms an emotional attachment to the drug of choice, making the experience feel pleasurable.

55
Q

How does the hippocampus influence drug addiction and relapse?

A

The hippocampus provides context dependence, meaning people may relapse when re-entering environments associated with previous drug use, even after rehabilitation.

56
Q

Why is overdose more likely in unfamiliar environments?

A
  • In familiar environments, the body adjusts to the drug (e.g., tolerance, metabolism) to reduce its effects.
  • In unfamiliar environments, these protective processes aren’t activated, increasing the risk of overdose.
57
Q

What are the key steps in the intracellular signaling pathways linked to drug addiction? (5)

A
  1. Dopamine and glutamate activate intracellular signaling pathways linked to drug addiction.
  2. NMDA receptors allow calcium (Ca²⁺) to enter neurons, activating:
    CaMKII in the cytoplasm.
    CaMKIV in the nucleus.
  3. Dopamine receptors activate cAMP, which activates Protein Kinase A (PKA).
  4. In the nucleus, PKA and CaMKIV phosphorylate CREB. Phosphorylated CREB recruits CBP (CREB-binding protein) and initiates gene transcription.
  5. The transcribed genes produce proteins that induce structural and functional changes in synapses, reinforcing addiction behaviors.
58
Q

What is the origin of cocaine and its initial uses?

A

Cocaine is derived from the leaves of the Erythroxylon coca plant and was initially used for medicinal purposes in Europe and as an additive in Coca-Cola.

59
Q

Why was cocaine used as a local anesthetic?

A

Cocaine was used for teething pain in infants because it blocks sodium channels, acting as an anesthetic at high doses.

60
Q

What are the sympathetic effects of cocaine? (3)

A

Tachycardia, vasoconstriction, and hypertension by activating the sympathetic nervous system.

61
Q

What are the effects of cocaine on users’ mood and behavior?

A
  • Euphoria, elevated self-confidence, and sensations similar to intense orgasm.
  • Increased sociability, but potential for dose-dependent aggression.
62
Q

How long does it take for the subjective high from cocaine to peak?

A

The subjective high from cocaine typically peaks around 30 minutes after use.

63
Q

Why is cocaine classified as lipophilic?

A

Cocaine is considered lipophilic because it can readily cross the blood-brain barrier, and affect the brain.

64
Q

How does the route of administration affect cocaine’s potency?

A

Cocaine’s potency varies depending on the route of administration, with intravenous use being the most immediate and oral has a delayed onset effect.

65
Q

How does cocaine affect dopamine in the brain?

A

Cocaine blocks the dopamine transporter (DAT), preventing dopamine reuptake and increasing its levels in the synapse.

66
Q

What other neurotransmitters does cocaine affect besides dopamine?

A

Cocaine also inhibits the reuptake of serotonin (5-HT) and norepinephrine (NE) at their respective transporters.

67
Q

Why are the addictive effects of cocaine attributed mainly to dopamine?

A
  • Although cocaine binds strongly to serotonin (5-HT) and norepinephrine (NE) transporters but causes addiction by blocking dopamine (DA) transporters.
  • This blockage leads to a buildup of dopamine in the brain, creating intense feelings of pleasure and reward that drive addiction.
68
Q

How quickly does cocaine block dopamine transporters (DAT) after administration?

A

Cocaine begins blocking dopamine transporters within 5 seconds, with peak inhibition occurring within 30 seconds.

69
Q

What brain region’s activity does cocaine increase to boost dopamine signaling?

A

Cocaine increases the activity of neurons in the Ventral Tegmental Area (VTA), which is a major source of dopaminergic inputs throughout
the brain

70
Q

What is the significance of transient dopamine release events, and how does cocaine affect them?

A

Dopamine release occurs in phases (on and off intermittently). Cocaine increases the frequency of these transient dopamine release events, enhancing feelings of reward and pleasure.

71
Q

What happens to cocaine’s effects if dopamine transporters (DAT) are removed or non-functional?

A

Mice lacking functional dopamine transporters (proteins that recycle dopamine) are immune to cocaine because cocaine relies on blocking DAT to cause dopamine buildup, proving DAT is essential for its effects.

72
Q

What does microdialysis measure in the brain?

A

Microdialysis measures neurotransmitters, like dopamine, floating freely in the brain’s extracellular fluid instead of being recycled.

73
Q

Where were microdialysis probes aimed in the cocaine study?

A

The microdialysis probes were aimed at the dorsal striatum, a brain region involved in habit formation and addiction behaviours

74
Q

What was observed about the relationship between cocaine and dopamine levels?

A

There was a close relationship between cocaine levels and rapid increases in extracellular dopamine, showing that cocaine quickly elevates dopamine in the dorsal striatum.

75
Q

How does cocaine affect dopamine in the nucleus accumbens?

A

Cocaine increases extracellular dopamine levels within the nucleus accumbens, a key area involved in reward processing.

76
Q

What is the role of the nucleus accumbens in addiction?

A

The nucleus accumbens processes reward saliency and motivation, generating the reinforcing effects of cocaine use.

77
Q

What happens when the nucleus accumbens is lesioned?

A

Lesions in the NAc reduce psychomotor symptoms (e.g., hyperactivity or repetitive movements) and repetitive cocaine use in rats.

78
Q

What did PET scans reveal about drug craving in addicts?

A

PET scans showed that viewing cocaine-related cues leads to increased dopamine release in the striatum, which is associated with heightened craving for the drug.

79
Q

What did participants do in the cocaine cue experiment?

A

Participants viewed neutral or cocaine-related cues, rated their subjective cravings, and underwent PET scans to measure brain activity.

80
Q

What was the key finding about the relationship between brain activity and craving?

A

Increased craving was positively correlated with higher brain activity in the DLPFC and medial temporal lobe during cocaine-related cue exposure.

81
Q

What happens to dopamine function in chronic psychostimulant users? (4)

A

Chronic psychostimulant use leads to decreased dopamine synthesis, lower dopamine per synaptic vesicle, and reduced dopamine release.

82
Q

How does tolerance develop with chronic cocaine use?

A

Tolerance develops because the same amount of cocaine no longer causes as strong a response due to changes in dopamine function and receptor activity.

83
Q

How does chronic use of cocaine affect dopamine receptors?

A

Chronic cocaine use lowers the number of D1 and D3 dopamine receptors in the striatum, making the brain less responsive to dopamine and requiring more cocaine to feel the same effect.

84
Q

What does the cellular basis for drug escalation suggest?

A

It suggests that chronic use leads to increasing drug usage because the same amount of the drug no longer produces the same effect.

85
Q

How does chronic psychostimulant use affect non-drug-related rewards?

A

Chronic psychostimulant use decreases the brain’s normal dopamine levels, leading to anhedonia, where everyday, non-drug-related activities feel less rewarding.

86
Q

Why is the absence of the drug aversive for chronic users?

A

Reduced dopamine activity makes the absence of the drug unpleasant, contributing to cravings and continued use.

87
Q

What are the effects of chronic cocaine use on dopamine signaling?

A

Similar effects are observed in the nucleus accumbens (NAc).
1. Reduced extracellular dopamine levels (less dopamine is released because neurons have fewer dopamine reserves)
2. Reduce intracellular dopamine levels (because neurons run out of dopamine to release)
3. Reduced autorecpetor sensitivity (neurons are less sensitive to regulating dopamine)
4. Reduced effects on DAT (Cocaine is less effective at blocking dopamine reuptake)
- Masks sensitization: Tolerance can hide the brain’s increased sensitivity to cocaine.

88
Q

How does cocaine use affect cognition?

A

Cocaine use is linked to attentional deficits, impulse control issues, poor decision-making, and working memory deficits.

89
Q

Which brain region is associated with cognitive impairments in cocaine users?

A

Cocaine use correlates with reduced gray matter in the prefrontal cortex (PFC), which is involved in cognitive functions.

90
Q

What cellular damage does cocaine cause in the brain similar to the effects of chronic stress? (3)

A

Cocaine causes dendritic spine loss, synapse loss, and neuronal death in the prefrontal cortex.

91
Q

How do amphetamines affect dopamine release?

A

Amphetamines increase dopamine release by:
1. Emptying dopamine storage: They push dopamine out of the storage vesicles into the cytoplasm
2. Reversing DAT: They make the dopamine transporter push dopamine out of the neuron into the extracellular space instead of reabsorbing it.

92
Q

What role does calcium play in the action of amphetamines?

A

Amphetamines increase calcium levels, which activates cAMP kinase II (CaMKII) and protein kinase C (PKC), leading to further dopamine release out into the synapse again.

93
Q

What is the effect of methamphetamine on dopamine-producing neurons?

A

Causes a loss of tyrosine hydroxylase immunoreactivity, an enzyme essential for dopamine production. This results in oxidative stress and neurotoxicity, leading to damage to dopamine-producing neurons.

94
Q

In which pathway is methamphetamine-induced dopamine neurotoxicity more pronounced?

A

Dopamine neurotoxicity is more pronounced in the nigrostriatal pathway (CPu) than in the mesolimbic pathway.

95
Q

How were the effects of methamphetamine studied in mice?

A
  • Mice received intraperitoneal injections (into the abdominal cavity for fast absorption) of methamphetamine
  • Mice were sacrificed 7 days later.
  • Brain sections were stained for tyrosine hydroxylase to evaluate dopamine neuron damage.

Neurobiology -BIOL4370 (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions