Drug Addiction Neural Circuitry: A Common Reinforcing Pathway

1
Drug Addiction Neural Circuitry A Common
Reinforcing Pathway?

• Courtney Mulligan
• 992558246
• Psy346

2
Introduction

• Drug abuse and dependence-
• increased allocation of behaviour towards
  drug-seeking behaviour
• decrease in more appropriate behavioural
  patterns.
• This transition is affected by brain
  processes.
• Theoretically, there are three ways in which
  drugs could interact with brain processes
• 1) drugs act as strong natural rewards
• 2) drugs change reward processes, for example,
  sensitization,
• 3) induce new brain processes, for example,
  aversive withdrawal states

3
Reward Pathway

• primarily the mesolimbic dopamine pathway
• medial forebrain bundle (MFB) has inputs into the
  ventral tegmental area (VTA), which has
  reciprocal connections with the nucleus accumbens
  (NAc) and limbic system.
• additional structures are involved in the
  expression of reward-related behaviour
• some researchers include the nigrostriatal
  pathway in the reward pathway
• involved in movement, such as the stereotypic
  responses seen in drug abuse
• the frontal cortex is also important in judging
  and planning

4
Neurotransmitters in the Reward Pathway

• Dopamine
• Increased activity in the VTA leads to increased
  dopamine release in the NAc
• Less important neurotransmitters that affect NAc
  dopamine
• GABAergic, serotonergic, cholinergic, and
  noradrenergic pathways, opioids, stress peptides,
  G-proteins, protein kinases, amine transporters,
  and transcription factors like cAMP
• hippocampus, and basolateral amygdala influence
  VTA activity, and consequently, and NAc dopamine
  levels through glutamate
• Nomikos et al. (1998)

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How the reward pathway interacts to produce
behaviour

• activation of the mesolimbic pathway
• part of the emotional circuit likely to motivate
  behaviours required for survival and reproductive
  success
• evolutionary importance for appropriate responses
  to be naturally rewarded for survival and fitness
• natural reinforcers
• food, water, parenting, sexual interactions
• dopamine
• reinforcement of behaviours
• blockade of mesolimbic DA impairs behavioural
  effectiveness of most reinforcers
• opioids
• important for set-point of hedonic value
• expression of reward and incentive related
  behaviours
• limbic system and frontal cortex
• planning and judgement
• memory and emotions are vivid
• Aids in the formation of context-specific cues

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Not just turning the reward pathway on

• appetite to consume versus working to obtain
• more about wanting than liking
• Berridge et al. (2003)
• Dopamine transmission
• Important to maintain instrumental responding
  over time, even in absence of primary
  reinforcement
• perceived hedonistic value
• the result of interaction with systems that
  represent physiological drive states
• opioid peptide transmission within the NAc
• increases hedonistic liking of food reward

7
Addictive Drugs, and Brain Structures

• humans have discovered how to stimulate this
  natural reward pathway artificially with drugs
• Effects of drugs on the mesolimbic pathway
• French and Rigel (2002)
• The involvement of brain areas outside the reward
  pathway
• Daunais et al. (2002)
• Cerebral blood flow increase in PFC
• fMRI activation of PFC and anterior cingulated
  nucleus in cocaine intoxication
• associated with subjective perception of
  intoxication reinforcing effects or enhanced
  mood.

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Addictive Drugs and Neurotransmitters

• addictive drugs mimic or enhance
  neurotransmitters active in the reward pathway
• neurotransmitter most clearly implicated is
  dopamine
• all addictive drugs regulate the dopamine
  activity of the VTA or NAc directly or
  indirectly, or through a second messenger system
  Gene expression, intracellular chemicals and
  molecular changes (signal transduction)
• directly
• alcohol
• D2 receptor and dopamine transporter
  densities alterations inhibit dopamine
  reuptake
• indirectly
• Opioids
• increase activity of VTA, and thereby
  increases NAc DA
• release via activation of mu-receptors
  located in GABA
• neurons within the VTA

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Addictive Drugs and Neurotransmitters Cont

• DA receptor blocking and destruction of the
  mesolimbic pathway
• some studies show an increase in
  self-administration, some a
• decrease
• Laviolette and van der Kooy
• the discrepancy therefore may be due to the
  differential effects of
• high and low doses of addictive drugs on reward
  
• all drugs affect dopamine, but drugs can
  also affect other neurotransmitters
• Other neurotransmitters mimicked or enhanced by
  addictive drugs in the reward pathway
• GABA, opioids, serotonergic, cholinergic,
  adrenanergic glutaminergic
• cocaine
• inhibit reuptake of serotonin, dopamine, and
  norepinephrine
• different actions of drugs depends on receptors
  outside this pathway
• cocaine? stimulates
• opioids ? sedate

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Interaction Between Drugs and the Brain to
Produce Behaviour

• drugs- immediate and powerful increase in
  activation of the reward pathway as compared to
  natural rewards
• increased dopamine? stronger reward
• reinforcing effects of psychostimulants are
  correlated with increases in dopamine
  concentrations in limbic regions
• Long term use of drug
• reinforcement of the drug gradually displaces
  other rewarding behaviours
• behaviour is increasingly driven by
  the effects of the drug
• not just in unconditioned rewarding properties
• drug associated stimuli acquire heightened
  abilities to influence behaviours

11
Interaction Between Drugs and the Brain to
Produce Behaviour Cont

• limbic system activation is also stronger
• increased emotional strength of memory
• emotions are paired with drugs reinforcement
• contextual cues can lead to strong cravings
• emotional and incentive learning process
• regions of frontal cortex involved in inhibitory
  response control are directly affected through
  chronic use
• Goldstein Volkow, (2002)

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Interaction Between Drugs and the Brain to
Produce Behaviour Cont

• Frontal lobe dysfunction makes the lure of the
  drug stronger and harder to resist
• overvaluing drug reinforcers
• undervaluing other reinforcers
• deficits in inhibitory control
• orbitofrontal and mesolimbic pathway dysfunction
• inability to inhibit inappropriate conditioned
  and unconditioned responses elicited by the drug,
  related stimuli, or internal drive states

13
Interaction Between Drugs and the Brain to
Produce Behaviour Cont

• drug seeking behaviour is based on two qualities
• increased incentive/motivation to seek out the
  reward
• Mesolimbic pathway
• impaired ability to inhibit responses
• Orbitofrontal lobes

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Conclusion

• addictive drugs hijack the reward system,
• the rewarding properties of drugs are stronger
  than the rewarding properties of natural rewards
• drug use effects the orbitofrontal lobes, leading
  to impairments in judgement and inhibition
• as a result, some people become focussed on this
  immediate, extremely rewarding behaviour to the
  exclusion of other less rewarding, but more
  adaptive behaviours

15
Future Research

• To obtain a fuller understanding of the
  relationship between reward and drug use,
  researchers need to expand beyond traditional
  limbic emphasis, and examine the structures and
  neurotransmitters involved in more distant
  aspects of reward, such as at the level of
  developing a behavioural response.
• the striatum and nigrostriatal pathway needs to
  be examined more closely
• the roles of the brainstem and other structures
  involved in physiological drive could be examined
  for how they affect the strength of liking or
  pleasure received from a reward
• Within the mesolimbic system itself, interactions
  of various neurotransmitters, especially in
  natural rewards, is not well understood
• The role of the HPA axis could also be examined
  further it is known that stress peptides are
  used in reward, but there does not seem to be
  much in-depth study of the interactions of the
  two systems
• The aversive effects of low doses of drugs in the
  reward pathway is interesting little research
  has been done to explain this dichotomy within
  the reward system