Lecture 9: Dopamine
Dopamine in reward and learning
Several competing accounts of dopamine function exist. We will examine whether dopamine is
important in:
• Pleasure
• Learning
o Promote learning via facilitation of synaptic plasticity
• Motivation
o DA motivates animals to want reward and engage in behaviours that bring about
rewards (goal-directed learning)
From first glance, these functions appear interrelated
The mid-brain dopamine system
DA is produced in two separate but anatomically close and related brain areas: VTA and SNc
Three different pathways from this brain areas where DA is produced, to where it is released to
potentially complete a function:
• Mesolimbic pathway: VTA—> amygdala, lateral septum, bed nucleus of the striatum
terminalis (NTS), hippocampus and NAcc
o Disorder in this pathway affect reinforced behaviours
o Key in emotion, learning and motivated behaviours
• Mesocortical pathway: VTA —> prefrontal cortex, entorhinal and cingulate cortex, and
hippocampus
o Disorder in this pathway has been linked with schizophrenia
• Nigrostriatal pathway: SNc —> caudate nucleus and putamen (dorsal striatum)
o Disorder in this pathway is associated with motor deficits seen in Parkinson’s disease
, Part 1 – Dopamine and Pleasure
(Hedonia Hypothesis)
Pleasure and the ‘pleasure centre’
Hypothesis that dopamine encodes pleasure for organisms when released in their brains
(Olds & Milner, 1954) (Olds. 1973) – Evidence that started off this theory and begun this topic of
research; Classic experiments
• Implanted stimulating electrodes in various regions of rat brains
• Looked whether the rat preferred to self-stimulate in those areas
o There were a series of brain areas that the animal wanted to stimulate so much,
they would do so to the point of forgoing performing basic behaviours (some
stimulated themselves to the point of starving to death)
o Interpreted that, the stimulation caused extreme pleasure to the extent that it took
priority over basic functions
Sites of rewarding brain stimulation (associated with mesolimbic areas):
• Some sites lie along a bundle of axons, known as the medial forebone bundle:
o Septal area
o Dorsal pons
o Lateral hypothalamus
o Medial forebrain bundle
• Sites within VTA itself, and projections
These areas are very closely related to the mesolimbic DA pathway
In humans, ex: (Heath, 1972; Portenoy et al. 1986)
The medial forebone bundle, among many other axons, contained the dopaminergic axons of the
VTA. The axons are projecting from the VTA via the mesolimbic system to other areas, such as NTS,
amygdala and nucleus accumbens.
These are all area where, if given the possibility, animals will enthusiastically self-stimulate.
Conclusion: Therefore, the theory arose that stimulation of these brain areas causes pleasure for
these animals (most straight-forward inference)
Is dopamine the pleasure neurotransmitter?
(Wise 1980, cited in Berridge 2007)
“The dopamine junctions represent a synaptic way station, where sensory inputs are translated into
the hedonic messages we experience as pleasure, euphoria and ‘yumminess’ “
• It is certainly the case that DA in the mesolimbic system, in many cases, correlates well
with subjective feelings of pleasure
Nucleus Accumbens
Focus on one area of the mesolimbic dopamine pathway, dopamine release in the NAcc
, NAcc is thought of in many ways as a ventral extension of the classical striatum system (caudate +
putamen + GP)
Because of its projections and connections to parts of the limbic system, as opposed to the
neocortex, it is intensely involved in learning and motivation and emotion, as opposed to control of
motor actions (striatum/BG)
One of the key pieces of evidence that dopamine encodes pleasure is that there is a strong
correlation between DA being released in the NAcc and experiences that feel pleasurable to us
Several stimuli that ‘feel good’ to humans increase DA levels in NAcc Commented [IM178]: Subject(s): rats
• (Bassareo & DiChiara, 1997) - eating food causes release of DA in NAcc; a basic, innately Methods: Measured by microdialysis
rewarding stimulus
• (Damsma, Day & Fibiger, 1989) - Nicotine causes release of DA in NAcc (pharmaceutical
stimulates that ‘feel good’)
• (Chen, Paredes, Li, Smith, Lowinson & Gardner, 1990) - Cannabis (application of THC, active
ingredient)
• (Wise et al. 1995) – Cocaine à increased DA concentration in NAcc
• (Pfaus, Damsma, Nomikos, Wenkstern, Blaha, Phillips & Fibiger, 1990) – Sexual behaviours
(measured in male rat after exposure and copulation with receptive females à dopamine
release in NAcc); another innately rewarding natural stimulus
General consensus of an association between increased levels of DA in NAcc and things that feel
pleasurable to humans
But is dopamine really encoding pleasure? Or can we find dissociations between the sensation of
pleasure/ happiness and this DA signalling in the NAcc?
Can we measure pleasure in animals?
(Berridge & Kringelbach, 2008) Commented [IM179]: Ken Berridge is a key pioneer in the field
of hedonia
It is important to measure pleasure (hedonia) in animals in an objective way, rather than just ‘do
they like to perform this action/do this behaviour to get a reward?’
Is this reward/ experience actually pleasurable?
• Berridge looked at facial expressions in rats, monkeys and humans, expressing hedonia from
the consumption of sweet foods
o Hedonic Reactions (sweet) - lip-licking behaviour
o Aversive Reactions (bitter) - open cry
Berridge argues that there are evolutionarily conserved mechanisms (at least across the
mammalian group) whereby you can see a similar series of facial expressions (motor actions) that
result from the consumption of pleasurable foods
This can be contrasted to equally conserved, but different facial expressions and motor patterns,
that occur when eating unpleasant/ bitter foods (aversive reactions)
To support that this is an innate evolutionarily conserved mechanisms, Berridge found an equation
that dictates how long this motor pattern lasts for:
Dopamine in reward and learning
Several competing accounts of dopamine function exist. We will examine whether dopamine is
important in:
• Pleasure
• Learning
o Promote learning via facilitation of synaptic plasticity
• Motivation
o DA motivates animals to want reward and engage in behaviours that bring about
rewards (goal-directed learning)
From first glance, these functions appear interrelated
The mid-brain dopamine system
DA is produced in two separate but anatomically close and related brain areas: VTA and SNc
Three different pathways from this brain areas where DA is produced, to where it is released to
potentially complete a function:
• Mesolimbic pathway: VTA—> amygdala, lateral septum, bed nucleus of the striatum
terminalis (NTS), hippocampus and NAcc
o Disorder in this pathway affect reinforced behaviours
o Key in emotion, learning and motivated behaviours
• Mesocortical pathway: VTA —> prefrontal cortex, entorhinal and cingulate cortex, and
hippocampus
o Disorder in this pathway has been linked with schizophrenia
• Nigrostriatal pathway: SNc —> caudate nucleus and putamen (dorsal striatum)
o Disorder in this pathway is associated with motor deficits seen in Parkinson’s disease
, Part 1 – Dopamine and Pleasure
(Hedonia Hypothesis)
Pleasure and the ‘pleasure centre’
Hypothesis that dopamine encodes pleasure for organisms when released in their brains
(Olds & Milner, 1954) (Olds. 1973) – Evidence that started off this theory and begun this topic of
research; Classic experiments
• Implanted stimulating electrodes in various regions of rat brains
• Looked whether the rat preferred to self-stimulate in those areas
o There were a series of brain areas that the animal wanted to stimulate so much,
they would do so to the point of forgoing performing basic behaviours (some
stimulated themselves to the point of starving to death)
o Interpreted that, the stimulation caused extreme pleasure to the extent that it took
priority over basic functions
Sites of rewarding brain stimulation (associated with mesolimbic areas):
• Some sites lie along a bundle of axons, known as the medial forebone bundle:
o Septal area
o Dorsal pons
o Lateral hypothalamus
o Medial forebrain bundle
• Sites within VTA itself, and projections
These areas are very closely related to the mesolimbic DA pathway
In humans, ex: (Heath, 1972; Portenoy et al. 1986)
The medial forebone bundle, among many other axons, contained the dopaminergic axons of the
VTA. The axons are projecting from the VTA via the mesolimbic system to other areas, such as NTS,
amygdala and nucleus accumbens.
These are all area where, if given the possibility, animals will enthusiastically self-stimulate.
Conclusion: Therefore, the theory arose that stimulation of these brain areas causes pleasure for
these animals (most straight-forward inference)
Is dopamine the pleasure neurotransmitter?
(Wise 1980, cited in Berridge 2007)
“The dopamine junctions represent a synaptic way station, where sensory inputs are translated into
the hedonic messages we experience as pleasure, euphoria and ‘yumminess’ “
• It is certainly the case that DA in the mesolimbic system, in many cases, correlates well
with subjective feelings of pleasure
Nucleus Accumbens
Focus on one area of the mesolimbic dopamine pathway, dopamine release in the NAcc
, NAcc is thought of in many ways as a ventral extension of the classical striatum system (caudate +
putamen + GP)
Because of its projections and connections to parts of the limbic system, as opposed to the
neocortex, it is intensely involved in learning and motivation and emotion, as opposed to control of
motor actions (striatum/BG)
One of the key pieces of evidence that dopamine encodes pleasure is that there is a strong
correlation between DA being released in the NAcc and experiences that feel pleasurable to us
Several stimuli that ‘feel good’ to humans increase DA levels in NAcc Commented [IM178]: Subject(s): rats
• (Bassareo & DiChiara, 1997) - eating food causes release of DA in NAcc; a basic, innately Methods: Measured by microdialysis
rewarding stimulus
• (Damsma, Day & Fibiger, 1989) - Nicotine causes release of DA in NAcc (pharmaceutical
stimulates that ‘feel good’)
• (Chen, Paredes, Li, Smith, Lowinson & Gardner, 1990) - Cannabis (application of THC, active
ingredient)
• (Wise et al. 1995) – Cocaine à increased DA concentration in NAcc
• (Pfaus, Damsma, Nomikos, Wenkstern, Blaha, Phillips & Fibiger, 1990) – Sexual behaviours
(measured in male rat after exposure and copulation with receptive females à dopamine
release in NAcc); another innately rewarding natural stimulus
General consensus of an association between increased levels of DA in NAcc and things that feel
pleasurable to humans
But is dopamine really encoding pleasure? Or can we find dissociations between the sensation of
pleasure/ happiness and this DA signalling in the NAcc?
Can we measure pleasure in animals?
(Berridge & Kringelbach, 2008) Commented [IM179]: Ken Berridge is a key pioneer in the field
of hedonia
It is important to measure pleasure (hedonia) in animals in an objective way, rather than just ‘do
they like to perform this action/do this behaviour to get a reward?’
Is this reward/ experience actually pleasurable?
• Berridge looked at facial expressions in rats, monkeys and humans, expressing hedonia from
the consumption of sweet foods
o Hedonic Reactions (sweet) - lip-licking behaviour
o Aversive Reactions (bitter) - open cry
Berridge argues that there are evolutionarily conserved mechanisms (at least across the
mammalian group) whereby you can see a similar series of facial expressions (motor actions) that
result from the consumption of pleasurable foods
This can be contrasted to equally conserved, but different facial expressions and motor patterns,
that occur when eating unpleasant/ bitter foods (aversive reactions)
To support that this is an innate evolutionarily conserved mechanisms, Berridge found an equation
that dictates how long this motor pattern lasts for:
