Chemical messengers - Dan Brierley Flashcards

Question

Study of ICSS and natural reward

Answer 1

In a study that compared lever pressing for brain stimulation and lever pressing for a natural reinforcer, when rats pressed a lever to inject a small quantity of chocolate milk into their mouths through an intraoral tube, they behave remarkably like self-stimulating rats. Reward processes all work via the same processes

Answer 2

1- Anterior Bed Nucleus project to Ventral Tegmental Area 2- vent teg to Nucleaus Accumbens (dopamine primary transmittor) 3- nuc acc to Ventral Pallidum and anterior bed nucleus of the MFB using enkephalin, an endogenous opioid neurotransmitter also involved - Amygdala and Raphe Nuclei amphetamine, cocaine, opiates, cannabis, ketamine all act on the NAc opiates, alcohol, barbiturates and nicotine all act on the ventral tegmental area.

Answer 3

motivation for reward, which includes both (1) incentive salience ‘wanting’ processes that are not necessarily conscious and (2) conscious desires for incentives or cognitive goals

Answer 4

ctual pleasure component or hedonic impact of a reward. Pleasure comprises two levels- (1) core ‘liking’ reactions that need not necessarily be conscious; (2) conscious experiences of pleasure

Answer 5

associations, representation, and predictions about future rewards based on past experiences. include (1) explicit and cognitive predictions and (2) implicit knowledge as well as well as associative conditioning

Answer 6

2 nd-stage dopaminergic fibres, and release of dopamine within the nucleus accumben were considered to directly mediate reward, or the experience of pleasure now consider that dopamine fibres are activated by wanted incentive stimuli and have an essential role in the acquisition and direction of natural reward- and drug-seeking behaviour Electrophysiological and microdialysis studies show that DA system activity is increased by the presence of natural rewards (food, water, sexual mates, etc), or stimuli that predict their availability – rather than by consummatory behaviour

Answer 7

genetic knockdown approach where a mutation in the dopamine transporter (DAT) in mice meant that levels of the transporter were significantly reduced, resulting in mutant mice having 70% elevated levels of synaptic dopamine. (As reuptake prevented) examined the consequences of the elevated synaptic dopamine on: (1) spontaneous food intake (2) incentive motivation and learning to obtain a palatable sweet reward in a runway task (3) affective “liking” reactions elicited by the taste of sucrose

Answer 8

Food intake of DAT slightly higher than wild-type mice over 4 week period. Mutant mice ate 21% more chow pellets average Their higher food consumption meant mutant mice had heavier body weights

Answer 9

Runway learning and performance for a food reward generates acquisition learning curves, as well as running speed and other measures of incentive motivation i.e measures of wanting. three compartments: a start box, a central runway and a goal box – which mice want to get to as contains sweet treat. Protocol starts by placing the mice in the goal box, then move the start box further and further away from the goal box so learn to run down to goal

Answer 10

1-3 habituation to apparatus 4-6 training 7-11 goal DAT knockdowns were faster, i.e. They reached the reward more quickly than wild types each day during the training phase (sessions 8–11). DAT knockdown mutant mice showed enhanced acquisition and incentive performance for a sweet reward in the runway task

Answer 11

The different taste-elicited affective reactions of mice and rats are the same as the affective facial reactions of human infants, great apes, and monkeys. - rhythmic tongue protrusions to sucrose indicating ‘liking’ - gapes to bitter tastes such as quinine, indicating ‘disliking’ DAT knockdown mice did not appear to “like” the taste of sucrose more than wild-type mice in the taste reactivity test, despite their higher incentive motivation or “wanting” for a sweet reward and higher food intake mutants actually displayed fewer liking reactions at the highest sucrose concentration

Answer 12

a variety of reinforcers including food/water, cocaine or intracranial self-stimulation (ICSS)

Answer 13

effects of varying reinforcer magnitude on cue-evoked dopamine release in the NAc shell in rats performing ICSS 1- trained to press a lever to receive ICSS 2- audio-visual cues that predict the lever being active, and therefore eliciting ICSS ( 2 second time interval between the cue and the lever becoming active) 3- observe dopamine activity : • Cue onset = small increase • Lever presented = bigger increase amplitude (i.e. how big) of cue-evoked dopamine release in the Nac reflects the magnitude of the predicted reinforcer

Answer 14

Very high magnitude reinforcer (compared to natural rewards) so elicits huge release of DA Cocaine molecule blocks DA reuptake by binding to DAT, further increasing DA signalling pronged mechanism on DA = very potent driver of ‘wanting’ behaviour = high risk of dependence

Answer 15

endocannabinoid system acting via CB1 receptors has modulatory influence over synaptic transmission blocking CB1 signalling by coadministering the CB1 ANTAGONIST rimonabant with cocaine reduces DA release in NAc CB1 antagonists reduce ‘wanting’ behaviour for cocaine and similar drugs

Answer 16

rats were injected with either the endocannabinoid anandamide, or THC from cannabis, and then feeding behaviour observed increasing doses of AEA reduced time until rats started feeding – i.e. increased their ‘wanting’ of food. AEA also increased number of meals and total intake, suggesting ‘liking’ of food may also be increased

Answer 17

enkephalin, which is an endogenous opioid.

Answer 18

consummatory aspects of reward - significant role for opioids to enhance liking reactions: opioid agonists suppress aversive reactions to bitter tastes and potentiate hedonic reactions to sweet taste evidence supports a crucialmrole for endogenous opioid systems in food reward - role in liking rather than wanting ie opioid antagonists (ie naloxone) reduce food intake by shortening meals,and human subjects report that previously palatable foods taste less pleasant

Answer 19

look at ability of morphine (opioid agonist) to modify sucrose palatability - assessed by the taste reactivity test rats injected with morphine (0.5/2/10mg) before receiving a 10-min intraoral infusion of 2% or 20% sucrose solution mean duration of ingestive reactions (i.e. tongue protrusion ‘liking’ responses) during each of two 5-min testing blocks

Answer 20

spent more time displaying ingestive reactions during an infusion of 20% sucrose than 2% sucrose solution, suggesting that the 20% is more palatable 2 mg/kg dose of morphine increased duration relative to control for both sucrose concentrations – opioid agonist increased sucrose palatability

Answer 21

opioid agonists increase liking - what about antagonists nalozone = antagonist f increasing doses of naloxone on 1-hour free-feeding with a palatable food

Answer 22

naloxone doses of 1 – 5 mg/kg consistently suppresses food consumption doses below 1mg/kg had no effect. opioid antagonists decrease ‘liking’ of food naloxone did not significantly influence other feeding related parameters: • latency to locate food source, • latency to feed, • average length of feeding bouts, • feeding rate doesn’t impact on the wanting mechanism – just the liking one. doesn’t affect the frequency of other behaviours (e.g. walking, grooming etc) - suggesting it’s only to do with food, it doesn’t slow other mechanisms

Answer 23

increasing opioid antagonist naloxone decreased the feeding stimulation elicited by THC increasing doses of naloxone alone slightly reduces food intake, but coadministration of CB1 antagonist rimonabant with naloxone significantly reduces intake. opioid and eCB systems interact to mediate ‘liking’ component of feeding