NROC61 - Central Reward systems

What is Reward?

Pleasurable response produced by a stimulus

Neural basis to check reward

intracranial self stimulation

drug self-administration

orofacial expressions

Intracranial self stimulation

Animals working for electrical stimulation of certain areas in the brain

Olds and Miilner 1954

Rats receive ICSS when they entered certain corner in a box and pressed a lever

ICSS Reinforcing Response

Preferred self-stimulation over eating/drinking

Mapping of reward pathways

ICSS Positive Sites

Medial forebrain bundle main region

Medial forebrain bundle is what?

Bundle of axons around VTA

Pleasure centre for self-stimulation

What happened with ICSS on MFB?

Increased response and consummatory behaviour

Stimulation of other limbic areas?

Produced lower rates of responding

less behaviour

ICSS Punishment Sites?

Periventricular system

Lower rates of responding where ICSS is avoided

ICSS Punishment sites

Forebrain, midbrain and brain stem, cerebellum, medulla

Other sites that support self-stimulation

Dopamine system

ICSS rates affected mostly by this

Dopamine receptor agonists (amphetamine)

Enhance rate of ICSS and lower reward threshold

Dopamine receptor antagonists (pimozide)

Lowers rate of ICSS and raises reward threshold

Infusion of Dopamine Blocker in the NAc

Decreases effects of reinforcing stimulation

Changes in rates of ICSS can reflect:

Rewarding effect, behaviour, motivation

Drug self-administration

Animals voluntarily self-administer drugs of abuse

Features of Drug self-administration

Tendency to self-regulate intake on low schedule of reinforcement

'binges' occur under unlimited access

Interference with dopamine synthesis?

Disrupts self-administration of drugs

Effect of Low doses of dopamine antagonists

increase response rates

Why do the drug response rates increase with dopamine antagonists?

Partial blockade decreases reinforcement, leading to compensatory responding

What else causes compensatory responding?

Lower doses of the drug

Depletion of 6-OHDA in NAc?

Abolished drug self-administration

What do dopamine antagonists do to the graph vs agonism?

Antagonist moves in right (more doses needed; decrease efficacy)

Agonist moves it left (fewer doses needed; increase efficacy)

What did micro dialysis studies show about drugs?

Reinforcing properties arise from the ability to augment mesolimbic DA release

ICSS vs Drug self-administration

ICSS increases rewarding effect

Effect of Self-administration is dose dependent

Where do drugs increase DA release?

Nucleus Accumbens (NAc)

Hedonia Hypothesis of Reward and Dopamine

All forms of reward, are mediated by mesolimbic dopamine system, even if sites are different

What causes anhedonia?

Disruption of DA pathway

Support for the Hedonia Hypothesis?

Place preference conditioning with drugs is attenuated by lesions of NAc

Animals prefer to be in the context of drugs

Other support for the Hedonia Hypothesis

Extracellular dopamine in NAc reduced during withdrawal

Individual variation in response to drugs

Support for Dopamine = Hedonia

Human PET study showed increased dopamine in brain from drugs

Binding to receptors due to drug administration

Lower raclopide binding means higher dopamine levels

What do higher DA levels appear as in behaviour?

Correlated with the feeling of high

Hedonic homeostatic dysregulation hypothesis

Drugs perturb hedonic "setpoint"

Initial euphoria from durgs violate homeostasis and are opposed by opposite processes

Another name for Hedonic homeostatic dysregulation hypothesis?

Opponent process theory

What happens during Opponent process theory?

After chronic use, Magnitude of getting High decrease tolerance to euphoric effect

Withdrawal grows bigger to maintain homeostasis

Environmental cues

Become Conditioned stimuli (CS) if associated with drug use

Can trigger response counter to the pleasure of the drug

What drives compulsive drug seeking?

Negative affective state caused by changing the set point of hedonia, increases incentive motivation

Which individuals prefer drugs?

Dysphoric (very unhappy), low arousal

Measuring Hedonic Reactions to Reward

Objective like and dislike reactions are homologous across species

Orofacial reactions to sweet/bitter

Dopamine and Orofacial reactions

lesions of mesolimbic DA system did not effect hedonic response to substances

Dopamine may mediate wanting

Wanting = incentive motivation to approach and consume reward

Incentive Salience hypothesis of DA function

Dopamine acts as an incentive salience attributor turning neutral stimuli into something that elicits 'wanting'

Dopamine is neither sufficient nor necessary for hedonic impact of natural rewards

Incentive Salience vs Hedonia

System is separable from 'liking; system for pleasure

Evidence of Incentive Salience hypothesis

DAT knock down mice had higher extracellular striatal DA

But they were willing to work harder and had enhanced acquisition for reward

Dopamine not involved in regulating hedonic effect of sucrose reward

What causes drug seeking according to IS hypothesis?

Excessive incentive salience attributed to drug stimuli due to sensitization of DA systems

Human area for ICSS

Humans emit high rate of ICSS in the septal area and centromedian thalamus

Preparatory vs consummatory behaviour

J shaped box apparatus to train rats to run for sucrose solution

Blocking of DA receptors reduces running speed and anticipatory activity but not sucrose intake

DAT knockout would increase speed however

Neural basis of liking

Opioid receptors in NAc shell