Drugs, Psychobiology and motivation

• cost of substance use

  • AUD/SUD one of largest contributors to premature death
  • high economic cost
  • are preventable
• how much of the population reports heavy drinking?

  18.4%
• what is difficult about unsanctioned drugs?

  harms and prevalence harder to keep track of
• what do chemical messengers do?

  • sense changes
  • process and transmit info
  • manage neural function
  • constantly adapt to changing context and needs
• what is phytochemistry?

  Study of plant chemicals

  • phytochemicals can act on receptors to produce psychopharmacological effects
• implications of human substance use

  • evolutionary past
  • adaptive benefits
  • survival advantage
  • almost every culture has substance for health or rituals
  • 'fourth-drive' (Siegel, 2005)
• how can drugs be administered?

  • oral ingestion
  • injection
  • inhalation
  • absorption through mucous membrane

  way its taken effects its effect
• oral administration

  • dissolves in stomach, carried to intestine -> absorbed into bloodstream
  • some pass through stomach wall
  • some metabolised by liver, reducing concentration
  • relatively safe
  • effects can be unpredictable
  • rate can depend on other factors
• injection

  • fast and predictable
  • subcutaneous, intramuscular, intravenous (taken straight to brain, quick)
  • no opportunity to counteract overdose, impurity and allergy
• inhalation

  • absorbed through capillaries in lungs
  • difficult to regulate dose inhaled
  • lung damage
• absorption through mucous membrane


  • in mouth, nose, rectum
  • cause damage to membrane
• drug penetration into CNS

  • drug enters bloodstream
  • must cross BBB
  • lipid soluble can dissolve in fatty membrane of brain and pass BBB
  • small molecules also pass through easier
• mechanisms of drug action

  • drugs can influence NS
  • some act on many membranes throughout CNS
  • some more specific and bind to receptors
• what is tolerance?

  a state of decreased sensitivity to a drug that develops because of use
• withdrawal

  • sudden elimination = adverse reactions
  • severity dependent on duration and degree of drug use, speed of drug being eliminated
• what is addiction?

  • 'substance use disorder' DSM V
  • 'harmful use', 'dependence syndrome' ICD-10
• what are SUDs?

  • chronically relapsing disorder
  • compulsion for drug
  • loss of control limiting intake
  • negative emotion when access prevented
• development of AUD/SUD

  experimental use -> casual use -> heavy use (misuse/abuse) -> dependence -> AUD/SUD
• drug use as a cost-benefit analysis (West, 2006)

  benefit:

  • pleasurable high, increased alertness, social aspects

  costs:

  • hangover, illness, death
• consequence of a free choice model

  • addicts are stigmatised
  • funding and research unnecessary - punitive response required
  • doesnt account for preference shift in addiction
• addiction is a disease

  • affect pathway deep in brain
  • cause pervasive changes in brain structure and function which persist even after stopping
  • the addicted brain different
• what are the implications for this claim?

  • shouldnt marginalise those with AUD/SUD
  • rather should try treating them, incarcerating them wont work
• key brain regions

  • mesocorticolimbic pathway - changes with SUDs
  • the reward circuit
• why do we look at the brain?

  if drugs had no effect on brain, would not experience pleasure etc. -> addiction would not exist
• key brain regions

  • mesocorticolimbic pathway - changes with SUD
  • the reward system
• what is the reward system in the brain?

  areas associated with reward, are affected when we experience any type of pleasure
• mesolimbic dopamine system

  the ventral tegmental area (VTA) and areas that project to and from it
• mesolimbic pathway

  VTA to limbic forebrain, also involves amygdala, hippocampus and bed nucleus of stria terminalis
• mesocortical pathway

  VTA to prefrontal cortex
• Nestler et al. (2005)

  all drug abuse stimulate dopamine release in mesolimbic system (directly or indirectly)
• what else stimulates the system?

  • food, sex, warmth and other 'natural' rewards

  dopamine does not = reward

  has many functions
• dopamine = reward?

  • over-simplistic view
  • originally, DA release -> pleasure, rewarding aspects
  • natural rewards also stimulate mesolimbic pathway -> good for survival
  • DA also triggered when drug-related cues are present
• the paradox

  • ind dependent on drugs want them but no longer like them
• Robinson and Berridge (e.g. 1993, 2008)

  argued dopamine important for wanting but not liking
• Incentive salience model of addiction

  Robinson and Berridge (1993, 2003)

  • dopamine attributes incentive salience to a stimulus, determines how important it is to the ind
• what does repeated drug use lead to

  sensitised spike in DA activity in mesolimbic pathway
• when is it also seen?

  when ind are exposed to drug related cues (Pavlovian conditioning)

  • drug cues have strong motivational properties -> increases wanting
• experiment 1

  Hobbs et al. (2005)

  separated ind into heavy and light drinkers. examined ratings of alcoholic and non alc drinks

  • no interaction between drinking status and type of drink on liking
• experiment 2

  manipulated wanting by a small priming dose of alc

  • no changes in liking for alc drink, but an increase in wanting
• incentive sensitisation theory: withdrawal and relapse

  • sensitisation process lasts long time
  • brain's neural system underlying wanting is sensitised, even after negative effects of withdrawal has diminished
  • long term sensitisation = enhanced, long term risk of relapse