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Substance abuse disorders Flashcards

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1
Q

What is substance abuse?

A

a pattern of drug use in which people rely on a drug chronically and excessively and not for therapeutic reasons

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2
Q

What does addiction/ dependence refer to?

A

being physically dependent on a drug in addition to abusing it

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3
Q

What is positive reinforcement?

A

• Positive reinforcement: the addition of a reinforcing stimulus following a behaviour that makes it more likely that the behaviour will occur again in the future
- Positive: addition of stimulant

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4
Q

What are the neural mechanisms of positive reinforcement?

A
  • Triggers the release of dopamine in the nucleus accumbens
  • Process of addiction begins in the mesolimbic dopaminergic system
  • Produce long term changes in other brain regions – starting with the ventral tegmental area (VTA)
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5
Q

Give features of positive reinforcement in drug use

A
  • Reinforcing stimuli have a greater effect if it occurs immediately after the behaviour
  • Drug users prefer heroin to morphine as heroin has a more rapid effect – it is more lipid soluble
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6
Q

What are the neural dopamine pathways?

A
  • Mesolimbic dopamine pathway
     Starts in ventral tegmental Area (VTA). Dopamine neurons project to nucleus accumbens
     Connects with nucleus accumbens (associated with striatum) and causes dopamine levels to rise
  • Mesocortical dopamine pathway
     Originates in VTA
     Travels to cerebral cortex (frontal lobes)
     Considered as part of the reward system
  • Dopamine levels increase reward seeking – it is released before stimulus
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7
Q

What are the neural mechanisms of positive reinforcement?

A
  • Changes in the VTA lead to increased activation in a variety of regions that receive dopaminergic input from the VTA
  • Synaptic changes that are responsible for the compulsive behaviours that characterise addiction occur only after continued use
  • The basal ganglia plays a critical role in instrumental conditioning (and movement – substantia nigra and Parkinson’s disease)
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8
Q

What structure in the basal ganglia is implicated in the neural changes we see as a result of substance abuse?

A

The dorsal striatum

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9
Q

What is negative reinforcement?

A

the removal of something unpleasant?

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10
Q

What is tolerance?

A

Decreased sensitivity from continued use?

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11
Q

What is withdrawal and what does it do?

A
  • Withdrawal symptoms
     Generally the opposite of the drug itself
     The body may have started to compensate for the disturbed homeostatic mechanisms
  • Potentially maintains addiction
     Withdrawal symptoms are unpleasant, taking the drug removes them, producing negative reinforcement
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12
Q

What may negative reinforcement explain?

A
  • Explanation for start of addiction in some scenarios

 Taking a drug to deal with stress or other problems

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13
Q

What are cravings due to?

A
  • Potentially due to long-lasting brain changes
  • Drug-related stimuli can elicit classically conditioned responses in substance abusers, both physiologically and subjectively – cravings
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14
Q

What was Frakens view on cravings?

A
  • Franken (2003) suggests craving and relapse are due to ‘attentional bias’ – cued by cognitive processes and increases in dopamine in response to drug stimuli
  • Franken’s (2003) review indicated dopamine increases in the nucleus accumbens (among other areas) in response to drug-related stimuli
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15
Q

What did Volkow use imaging to show?

A

dopamine increased in relation to cocaine-cues in the dorsal striatum but not the ventral striatum (where the nucleus accumebens is located)

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16
Q

Apart from dopamine what else is implicated in substance abuse?

A

• Prefrontal cortex has also been implicated

- Amount of activation of prefrontal cortex is inversely related to cocaine use

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17
Q

What are features of heroin use?

A
  • Needle use
  • Transmission to unborn child (child will be born addicted to drug)
  • Uncertainty of strength and what it can be mixed with
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18
Q

What type of drug is heroin?

A

An opiate

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19
Q

What does stimulation of opiate receptors cause?

A

 Analgesia (periaqueductal grey matter) – pain relief
 Hypothermia (preoptic area)
 Sedation (mesencephalic reticular formation)
 Reinforcement (ventral tegmental area and nucleus accumbens)

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20
Q

What do opiate related stimuli to?

A

trigger the release of dopamine in the nucleus accumbens (NAC)

21
Q

What did Wise et al. (1995) find about levels of dopamine in rats in regards to heroin?

A

increases of 150-300% in levels of dopaimine in rats’ NAC while the rat pressed a lever that delivered heroin
 Rats will also press a lever to inject opiates into the NAC or the ventral tegmental area – suggesting that the reinforcing effects of opiates are produced by the activation of neurons in the mesolimbic system and release of dopamine in the NAC

22
Q

Give features of Cocaine and amphetamines

A
  • Cocaine and amphetamines have similar behaviour effects but their sites of action are different
  • Likely highly addictive – Bozath & Wise (1985) reported that rats that self-administered cocaine were 3 times more likely to die than rats who self-administered heroin
  • Blocking dopamine receptors or destroying dopaminergic terminals in the NAC causes cocaine and amphetamines to lose much of their reinforcing effect
  • Highlights role or mesolimbic system
  • These drugs have quick acting reinforcing effects
23
Q

What does cocaine do?

A

Deactivates dopamine transporter proteins, blocking the reuptake of dopamine

24
Q

What does amphetamine do?

A

Also inhibits the reuptake of dopamine but directly stimulates the release of dopamine from terminal buttons as well

25
Q

Is smoking addictive and how do we know?

A

Yes

  • Evidence that it is highly addictive, e.g. continuing to smoke after a heart attack, cancer surgery etc.
  • Animals will also self-administer nicotine
26
Q

What does smoking stimulate?

A

Nicotinic acetylcholine receptors

27
Q

What is nicotine associated with that reinforces smoking behaviour?

A

the release of dopamine in the NAC, reinforcing the behaviour

28
Q

Damage to what area disrupts smoking addiction and how do we know??

A

Damage to the insula
- Naqvi et al. (2007)
 19 smokers with insula damage following acquired brain injury
 50 smokers with no insula damage following acquired brain injury
 No difference in whether or not they had quit when they participated in the study
 However, those who had insular damage were significantly more likely to have a disruption of smoking addiction
- Insula shows highest association with smoking cessation

29
Q

What are potential effects of alcohol?

A

 Mild euphoria (positive reinforcement)
 Anxiolytic: reduces the discomfort of anxiety
 Disinhibition (behaviour differs depending on the situation in which the individual consumes the alcohol)
 Alcohol myopia: tendency for people to respond to near and immediate cues while ignoring more remote cues and potential consequences

30
Q

What does alcohol do?

A

Increases activity in the dopaminergic neurons of the mesolimbic system

31
Q

What are the two major sites of action with alcohol?

A

 Indirect antagonist at NMDA receptors

 Indirect agonist at GABBAA receptors (anxiolytic and sedative effects)

32
Q

What can the removal of alcohol trigger and why?

A
  • Increased sensitivity of NMDA receptors after suppressive effect of alcohol is removed can trigger seizures and convulsions (withdrawal symptoms)
  • Drugs which block NMDA receptors were shown to prevent the seizures in mice
33
Q

Apart from the dopaminergic system what is the reinforcing effect of alcohol also due to?

A
  • Alcohol can also trigger the release of endogenous opioids
  • Several studies have shown that drugs that block opiate receptors also block the reinforcing effects of alcohol in a variety of species, including rats, monkeys, and humans
  • The level of opioid receptors increases with abstinence and is thought to be related to cravings for alcohol
34
Q

What is Korsakoff syndrome, who is it seen in and what happens with it?

A
  • Often seen in alcoholics who are malnourished
  • Caused by a lack of vitamin B1 in the brain and exacerbated by the toxic effects of alcohol
  • Damage to areas of the thalamus and the mammillary bodies – structures important for encoding new memories
  • Type of amnesia
35
Q

What receptors mediate most of the psychotropic effects of THC?

A

Cannabinoid type 1 (CB1) receptors

36
Q

What does blocking CB1 receptors do?

A

Abolishes the high produced by smoking cannabis

37
Q

What effect does THC have on dopaminergic neurones?

A

Stimulating effect

38
Q

Apart from in cannabis what else do CB1 receptors have an effect on?

A
  • CB1 receptors also have a probable role in the reinforcing effects of other drugs as well as cannabis
     Blocking CB1 receptors in mice can abolish the reinforcing effect of cannabis, morphine and heroin and reduce the reinforcing effects of alcohol
     Rimonabant, a drug which blocks CB1 receptors, decreases the reinforcing effects of nicotine
39
Q

In large doses what does THC produce?

A

In large doses THC can produce anxiety and psychotic behaviours

40
Q

What does CBD do?

A
  • CBD has anti-anxiety and anti-psychotic effects. Doesn’t produce a high
  • Lots of evidence looking into CBD as a therapeutic drug
41
Q

What influences whether someone is likely to take a substance and their likelihood of becoming dependent?

A

Genetic and environmental factors

42
Q

What was Kendler et al.’s (2003) experiment about the specificity of genetic and environmental risk factors for use and abuse/dependence of 6 classes of illicit substance?

A

 Interviews of 1,196 male-male twin pairs
 Found that environment plays a stronger role in drug use but genetics plays a stronger role in determining whether the person becomes addicted

43
Q

What percentage is it estimated that the vulnerability to addiction can be attributed to genetic factors?

A
  • It is estimated that 40-60% of the vulnerability to addiction can be attributed to genetic factors
  • Includes both variability in metabolism of the drug and variability in the sensitivity to the reinforcing effects
44
Q

What environmental factors influence addiction?

A

Drug availability, low SES, poor parental support, stress

45
Q

How is opiate addiction commonly treated?

A
  • Opiate addiction is most commonly treated with methadone, an orally administered replacement drug
  • A newer drug, buprenorphine blocks the effect of opiates and produces only a weak opiate effect (buprenorphine + naloxone shown to be particularly effective – very limited abuse potential. If take heroin whilst on this combination withdrawal effects produced)
46
Q

What is immunotherapy?

A

Vaccines specific to the substance abused (reward potential for specific substance becomes limited)

47
Q

What is deep brain stimulation in regards to therapy for drug use?

A

DBS of the NAC had some promising effects, however it is a high risk procedure

48
Q

Give features of TMS in terms of therapy for drug use

A

TMS is less invasive than DBS and has shown efficacy in reducing tobacco use but the effects on nicotine use diminished over time

Brain and Behaviour (11 decks)

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