Pleasure
The dopamine neurons projecting from the VTA to the nucleus accumbens are believed to play an important role in "reward". Some investigators believe that when you experience pleasurable events, you can thank dopamine release in the nucleus accumbens for the reward experience. Cocaine and amphetamine both elevate dopamine levels in the brain. It is believed that the powerfully-reinforcing and rewarding properties of cocaine and amphetamine are due to this increase in brain dopamine activity. Of course, dopamine neurons did not evolve to mediate cocaine reward, but presumably evolved to mediate the reinforcing effects of natural rewards, such as food, water and sex. Drugs like cocaine and amphetamine presumably produce their reward effects by artificially tapping into this neuronal system that evolved to mediate natural reward processes.
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Other investigators are more conservative, and point out that most of our
knowledge about dopamine function comes from studies in rats. Since the rat
cannot directly tell us when he/she is experiencing pleasure, we know only that
when dopamine activity is disrupted, normally rewarding events (food, water,
sex, cocaine, amphetamine) seem to lose their reinforcing properties (that is,
the ability to cause a repetition in the behavior that preceded their
occurrence). For example, teach a rat to press a lever in order to receive
food. Later, administer a drug that blocks dopamine receptors in the brain (a
dopamine antagonist). After initially pressing the lever for food, the rat soon
gives up pressing, as if the food were no longer reinforcing.
Dopamine neurons projecting to the striatum are implicated in motor functions. A loss of these "nigrostriatal" dopamine neurons is the cause of Parkinson's disease (tremors, rigid movements, difficulty initiating movements). As you might imagine, a rat under the influence of a dopamine antagonist drug is likely to show some impairment in its ability to perform operant responses, like lever-pressing. Therefore, if the rat under the influence of a dopamine-blocking drug stops lever-pressing for food, it is difficult to determine whether this is because the food has lost its reinforcing propertes or whether it is because it is now more difficult to perform the operant response. For an experimental methodology to disentangle these reward and motor explanations see Representative Publications: Horvitz and Ettenberg (1989)
Dopamine and Schizophrenia
Another issue in the dopamine story is that dopamine is implicated in
schizophrenia. Almost all "antipsychotic" drugs prescribed for
schizophrenics are dopamine antagonist drugs. Individuals who overdose on
amphetamine and cocaine (dopamine agonistdrugs)
often develop psychotic symptoms (hallucinations/delusions) which are
indistinguishable from those of schizophrenics. Given dopamine's role in motor
and reinforcement functions, why would dopamine overactivity
produce schizophrenic symptoms? One strong possibility is that dopamine release
to certain brain regions occurs when you are "attending" to salient
events. Representative Publications: Horvitz,
Stewart, and Jacobs (1997); Horvitz (2000)
An overactivity of dopamine at these sites may produce attentional abnormalities, so that stimuli which would normally be ignored are instead considered to be relevant. This is exactly what many schizophrenia researchers believe occurs in schizophrenics. Stimuli that you would normally ignore (for instance background sounds that you are ignoring as you read this discussion, or were ignoring) are not filtered-out in schizophrenics. These "irrelevant" events enter consciousness as salient events, and delusional schemes are developed to "explain" the significance of these events.
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Dopamine Anatomy
If you were to start from the bridge of your nose, and move backwards into
the brain, you would find the two neighboring sites where most brain dopamine
neurons originate, the substantia nigra (SN) and the ventral tegmental area
(VTA).
The
dopamine neurons originating in the VTA send their axons to the prefrontal
cortex (an area implicated in attention and working memory) and to the nucleus
accumbens (associated with motivational functions). The dopamine neurons in the
SN project to the striatum (associated with motor function).
Representative Publications ( below the publications are simply summaries, not abstracts).
- Wickens,
J., Horvitz, J.C., Costa, R., Killcross, S. Dopaminergic Mechanisms in Actions and Habits, Journal
of Neuroscience, 27, 8181-3, 2007.
A review of recent work at cellular and
behavioral levels of analysis relevant to dopamine’s role in the learning
and performance of goal-directed behaviors and S-R habits.
- Horvitz, J.C., Choi, W., Morvan, C., Eyny,
Y. Balsam, P.D. A “Good Parent” function
of dopamine: transient modulation of learning and performance during early
stages of training.
The paper describes a theoretical perspective on dopamine’s
role in the learning and performance of goal-directed behavior. Recent work in our laboratory suggests that
dopamine plays a critical role in both learning and performance of behaviors
during early stages of training, and that dopamine’s contribution to behavioral
performance diminishes as the behavior becomes a well-acquired habit.
- Rick, J.H., Horvitz, J.C., Balsam, P.D. The Effect of Dopamine Receptor Blockade on Behavioral Variability and Comparisons to Extinction, Behavioral Neuroscience, 120, 488-92, 2006.
It has long been held that reductions in dopamine
transmission reduce the ‘reward’ value of reinforcers. Following dopamine receptor blockade, animals
show reduced rates of operant responding similar to those seen in animals for whom reward delivery is omitted, i.e., animals show what appears
to be behavioral ‘extinction’.
However, during extinction, animals show not only reduced operant
response rates but also an increase in behavioral variability. This paper
demonstrates that while dopamine receptor blockers reduce rates of reinforced
responding, they do not produce the increase in response variability that
characterizes extinction.
- Horowitz, T.S., Choi, W., Horvitz, J.C., Cote, L.J., Mangels, J.A. Visual search deficits in Parkinson’s disease are attenuated by bottom-up target salience and top-down information, Neuropsychologia, 44, 1962-77, 2006.
Dopamine neuronal responses appear to play an important
role in marking environmental stimuli as ‘salient’, i.e., promoting
basal ganglia and frontal cortical processing of particular stimuli in the
environment. This paper is a detailed examination of the attentional
difficulties that arise in patients that have suffered a loss of nigrostriatal
dopamine neurons.
- Stern E.R., Horvitz, J.C.,
This paper examines aspects of motor difficulties in Parkinson's pattients, a group that suffers loss of nigrostriatal dopamine neurons.
- Choi, W., Balsam, P.D., Horvitz, J.C. Extended Habit Training Reduces Dopamine Mediation of Appetitive Response Expression, Journal of Neuroscience, 25, 6729-33, 2005.
While dopamine plays a key role in the performance of
goal-directed behaviors, this role diminishes as the behavior has become an overlearned 'habit'.
- Davidson, M.C., Horvitz, J.C. Tottenham, N. , Fossella, J.A. Watts, R. Ulug, A.M. and Casey, B.J. Differential cingulate and caudate activation following unexpected nonrewarding stimuli, Neuroimage, 23, 3, 1039-45, 2004.
Neuronal activity in two dopamine target regions in humans, the dorsal striatum and anterior cingulate, is modulated by violations in the expectations of rewarding and non-rewarding events.
- Eyny, Y.S. and
Horvitz, J.C. Opposing roles of D1 and D2 receptors in appetitive
conditioning. Journal of Neuroscience, 23, 1584-87, 2003.
There are two 'families' of dopamine receptors, D1 and
D2. These receptors have different structures, and dopamine binding to D1
versus D2 receptors produce different, and in some cases opposite, effects on
intracellular events (such as cyclic AMP production). This paper shows that D1
and D2 receptors also play opposing roles in simple associative learning.
- Horvitz,
J.C. Dopamine, Parkinson’s disease, and volition. Commentary in Behavioral
and Brain Sciences, 25(5), 586, 2002.
- Horvitz, J.C. Dopamine gating of glutamatergic sensorimotor and incentive motivational inputs to the striatum. Behavioral Brain Research, 137, 65-74, 2002.
This paper suggests a means by
which dopamine's motivational and sensori-motor
functions can be viewed as the result of a single fundamental mechanism, i.e.,
the modulation of glutamate inputs from limbic and sensori-motor
brain regions.
- Horvitz, J.C. and Eyny, Y.S. (2000) Dopamine D2 receptor blockade reduces response likelihood but does not affect latency to emit a learned sensory-motor response: Implications for parkinson's disease. Behavioral Neuroscience , 114 (5), 934-939.
Reductions in brain dopamine activity produce reductions in movement. Interestingly, however, this reduction in movement is seen in some instances and not in others. Parkinson's patients suffer a loss of most of their nigrostriatal dopamine neurons. There is a well-known anecdote about the Parkinson's patients in the hospital who have great difficulty walking. However, when a fire breaks out in the hospital, the Parkinson's patients walk quickly out of the building, with little difficulty. (Patients with spinal cord injuries affecting leg movement could not do so). Dopamine plays a role in the ability to move, but the nature of its role is unclear. Dopamine does not seem to be necessary in order to perform a movement in response to a "strong eliciting stimulus" (e.g., the fire alarm). The paper above shows that rats under the influence of a dopamine receptor-blocking drug will show normal movement when presented with a strong (in this case, well-learned) eliciting stimulus, but will show severe deficits when the same movement requires internal generation.
- Horvitz, J.C. (2000) Mesolimbic and nigrostriatal dopamine responses to salient non-reward events. Neuroscience, 96, 651-656. ( pdf link )
Dopamine neurons of the mesolimbic and nigrostriatal systems respond to reward events. However, these neurons also respond to other types of salient events. The midbrain dopamine neurons appear to become activated by events whose salience derives from primary or conditioned reward properties, novelty, aversive properties, conditioned aversive properties, or physical intensity (e.g., loudness, brightness, rapid onset). The fact that midbrain dopamine neurons are driven by a wide category of salient environmental stimuli suggests that, while dopamine activity plays a role in reinforcement or incentive motivational processes, dopamine neurons do not carry a reward signal to target regions of the brain.
- Horvitz, J.C., Sterwart, T., and Jacobs, B.L. (1997) Burst activity of ventral tegmental dopamine neurons is elicited by sensory stimuli. Brain Research , 759, 251-258. ( PDF link )
Dopamine neurons in the ventral tegmental area (VTA) are widely believed to provide a reward signal. Indeed, VTA dopamine neurons respond to reward events, like food or conditioned stimuli signalling food delivery. However, this paper demonstrates that the VTA dopamine neurons also respond to salient sensory events which are not rewarding or reward-related. The paper discusses the possiblity that mesolimbic dopamine activity may play a role in attentional processes, rather than a specific role in reward.
- Horvitz, J.C.,
Animals under the influence of dopamine antagonist drugs show reduced rates of responding for natural rewards such as food and water. However, it is possible that these reductions in motivated behavior reflect a drug-induced blunting of primary motivational states, hunger and thirst, rather than reducing the reward properties of the reinforcer. This paper demonstrates that dopamine disruptions do not reduce thirst. Reductions in water-reinforced behavior seen in dopamine-disrupted animals (Ettenberg and Horvitz 1990), then, cannot be accounted for by reductions in the animal's primary motivational state.
Horvitz, J.C. and Ettenberg, A. (1991) Conditioned incentive properties of a food-paired conditioned stimulus remain intact during dopamine receptor blockade. Behavioral Neuroscience, 105, 536-541.
Investigators have suggested that dopamine activity may underlie the ability of conditioned incentive stimuli (events that have previously been associated with primary rewards) to activate and motivate behavior. According to this view, dopamine would not mediate the reinforcing effect of cocaine, but instead would underlie the motivational/arousing effects of seeing, say, the cocaine-spoon. This study asked whether stimuli that have previously been paired with reward, maintain their motivational/arousing (conditioned incentive) properties even when brain dopamine activity has been disrupted. The results indicate that while dopamine receptor blockade reduces overall levels of behavioral activity, it does not specifically attenuate the incentive properties of conditioned stimuli previously paired with reward.
- Horvitz, J.C. and Ettenberg, A. (1989) Haloperidol blocks the response-reinstating effects of food reward: A methodology for separating neuroleptic effects on reinforcement and motor processes. Pharmacology, Biochemistry, and Behavior , 31, 861-865.
This study introduces a methodology for asking whether dopamine antagonists disrupt reinforcement, without the motor confound that usually clouds such investigations. Rats run down a straight-arm alley to receive food reward in a goal box. After animals have acquired the running behavior, they undergo a series of extinction trials until running speeds have slowed again. Nondrugged animals will show a reinstatement of the running behavior after a single additional reinforcement trial. This response-reinstatement is blocked in animals under the influence of a dopamine antagonist drug during the reinforced trial. Since all animals are tested 24 hr after the reinforcment/drug trial, drug-induced motor artifacts cannot account for these results. The results provide evidence for a dopamine involvement in food reinforcement. The methodology introduced in this paper has subsequently been employed to investigate dopamine involvement in the reinforcing properties of water, cocaine, amphetamine, and heroin.
For an overiew of the current state of the dopamine literature, placing the work above in some context, see the following review article:
- Getting the brain's attention: Rather than signaling pleasure as previously thought, the neurotransmitter dopamine may be released by brain neurons to highlight significant stimuli, Science, Oct 3 1997, 278, 35-37.
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