1. M.B.B.S,M.C.P.S.(Psych),F.C.P.S (Psych).
Reward.
DR.M.ISHAQUE SARHANDI.
M.B.B.S,M.C.P.S.(Psych),F.C.P.S (Psych).
Coordinator Psychiatry, Neurology, HLHE and Head Students’ Counseling Unit.
Sulaiman Al-Rajhi Colleges, Bukayria, Qaseem, KSA.

2. History of Reward System:
James Olds and Peter Milner were researchers who found the reward system in They discovered, while trying to teach rats how to solve problems and run mazes, stimulation of certain regions of the brain.
Where the stimulation was found seemed to give pleasure to the animals.
They tried the same thing with humans and the results were similar.

3. Definition of Reward System:
A positive emotional stimulus. In psychological terms, a reward is reinforcing — it promotes repeated responding to obtain the same stimulus. In neuroscience, the reward system is a collection of brain structures that are responsible for reward-related cognition,
Including positive reinforcement and both "wanting" (i.e., desire) and "liking" (i.e., pleasure).

4. Reward is the attractive and motivational property of a stimulus that induces appetitive behavior – also known as approach behavior – and consummator behavior.
 In its description of a rewarding stimulus (i.e., "a reward"), a review on reward neuroscience noted,
"any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward.“
 In operant conditioning, rewarding stimuli function as positive reinforcers. 

5. Primary rewards are those which are necessary for the survival of a species, and include homeostatic (e.g., palatable food) and reproductive (e.g., sexual contact) rewards.
Intrinsic rewards are unconditioned rewards that are attractive and motivate behavior because they are inherently pleasurable.
 Extrinsic rewards, such as money, are conditioned rewards that are attractive and motivate behavior, but are not pleasurable.

6. Extrinsic rewards derive their motivational value as a result of a learned association (i.e., conditioning) with intrinsic rewards.
Rewards are generally considered more desirable than punishment in modifying behavior.

7. Anatomy of Reward system:
 The reward system includes the brain structures and Pathway or tracts: 

8. Anatomy of Reward system: ( Structures):
Ventral tegmental area,
Nucleus accumbens,
Dorsal striatum (i.e., caudate nucleus and putamen), 
Substantia nigra (i.e., the pars compacta and pars reticulata),
Prefrontal cortex, 
Anterior cingulate cortex, 
Insular cortex, 
Hypothalamus, 
Thalamus (multiple nuclei), 
subthalamic nucleus,
Globuspalliduis,
 ventral pallidum, 
parabrachial nucleus,
And Amygdala,
Hippocampus, 

9. Pathways:
 Mesolimbic dopamine pathway, which connect the ventral tegmental area(VTA) to the nucleus accumbens (NAcc),  in these pathways, dopamine acts on D1-like receptors or D2-like receptors to either stimulate (D1-like) or inhibit (D2-like) the production of cAMP.
The associated GABAergic D1-type medium spiny neurons in the nucleus accumbens shell, is a critical component of the reward system that is directly involved in the immediate perception of the motivational component of a reward (i.e., "wanting").
The glutamatergic projection nuclei in the sub-thalamic nucleus, prefrontal cortex, hippocampus, thalamus, and amygdala connect to other parts of the reward system via glutamate pathways.
 The medial forebrain bundle, which is composed of monoamine neurons that project from several distinct nuclei, is also part of the reward system.

10. The glutamatergic projection nuclei in the sub-thalamic nucleus, prefrontal cortex, hippocampus, thalamus, and amygdala connect to other parts of the reward system via glutamate pathways.
 The medial forebrain bundle, which is composed of monoamine neurons that project from several distinct nuclei, is also part of the reward system.

12. Mesolimbic dopamine pathway, reward and negative symptoms:
When a patient with schizophrenia loses motivation and interest, and has anhedonia and lack of pleasure, such symptoms could also implicate a deficient functioning of the mesolimbic dopamine pathway, not just deficient functioning in the meso cortical dopamine pathway.
This idea is supported by observations that treating patients with antipsychotics, particularly the conventional antipsychotics,

13. can produce a worsening of negative symptoms and a state of “neurolepsis” that looks very much like negative symptoms of schizophrenia.
Since the prefrontal cortex does not have a high density of D2 receptors, this implicates possible deficient functioning within the mesolimbic dopamine system causing inadequate reward mechanisms,
This is exhibited as behaviors such as anhedonia and drug abuse, as well as negative symptoms, exhibited as lack of rewarding social interactions, and lack of general motivation and interest.

14. Perhaps the much higher incidence of substance abuse in schizophrenia than in healthy adults, especially of nicotine but also of stimulants and other substances of abuse,
Could be partially explained as an attempt to boost the function of defective mesolimbic dopaminergic pleasure centers, perhaps at the cost of activating positive symptoms.

15. Stress and reward system to the development of mood disorders:
Mood disorders are common and debilitating conditions characterized in part by profound deficits in reward-related behavioral domains.
A recent literature has identified important structural and functional alterations within the brain's reward circuitry — particularly in the ventral tegmental area– nucleus accumbens pathway — that are associated with symptoms such as anhedonia and aberrant reward-associated perception and memory. 

16. The brain’s reward circuitry:
The best characterized reward circuit in the brain comprises dopaminergic neurons in the ventral tegmental area (VTA) that project to the nucleus accumbens (NAc), which is part of the ventral striatum. The principal neurons of the NAc are GABAergic medium spiny neurons (MSNs).
This VTA–NAc circuit is crucial for the recognition of rewards in the environment and for initiating their consumption, but these regions respond to aversive stimuli as well (see below for further discussion).
VTA dopaminergic neurons also innervate several regions of the prefrontal cortex (PFC), central amygdala, basolateral amygdala (BLA) and hippocampus, as well as other areas (FIG. 1 ).

17. All of these so-called ‘brain reward regions’ are inter-connected in complex ways: for example,
the NA receives dense glutamatergic innervation from the PFC, amygdala and hippocampus; and the PFC, amygdala and hippocampus form reciprocal glutamatergic connections with one another.
The functional output of each of these regions is modulated by several types of GABAergic interneurons and, in the NAc, by cholinergic interneurons as well.

18. Depressive disorders affect ~20% of people in the United States within their lifetime, and roughly one-half of patients do not fully respond to available treatments. The behavioral symptoms of depression are extensive, covering emotional, motivational, cognitive and physiological domains.
Large subsets of patients with these disorders exhibit deficits in several aspects of reward, as defined by responses to positive emotional stimuli such as food, sex and social interaction.

19. Prominent among these reward deficits is anhedonia
Prominent among these reward deficits is anhedonia. Depression is highly comorbid with anxiety, and it has been estimated that over 20% of individuals with a mood or anxiety disorder also fulfil criteria for drug addiction and, conversely, that 30–40% of individuals suffering from addictive disorders have a comorbid mood or anxiety disorder3.
These considerations suggest a large degree of overlap among the brain regions affected in depression and those affectedin drug addiction.

20. Indeed, increasing evidence in humans and animals suggests that mood disorders and drug addiction are associated with major disruptions within the brain’s reward circuitry.

21. The brain’s reward circuitry:
The best characterized reward circuit in the brain comprises dopaminergic neurons in the ventral tegmental area (VTA) that project to the nucleus accumbens (NAc), which is part of the ventral striatum.
The principal neurons of the NAc are GABAergic medium spiny neurons(MSNs). This VTA–NAc circuit is crucial for the recognition of rewards in the environment and for initiating their consumption, but these regions respond to aversive stimuli as well (see below for further discussion).
VTA dopaminergic neurons also innervate several regions of the prefrontal cortex (PFC), central amygdala, basolateral amygdala (BLA) and hippocampus, as well as other areas (FIG. 1 ).

22. All of these so-called ‘brain reward regions’ are inter- connected in complex ways: for example, the NAc receives dense glutamatergic innervation from the PFC, amygdala and hippocampus; and the PFC, amygdala and hippocampus form reciprocal glutamatergic connections with one another.
The functional output of each of these regions is modulated by several types of GABAergic interneurons and, in the NA, by cholinergic interneurons as well.

41. Thank U.