Neurobiology and neurochemistry or reward based behaviours Flashcards Preview

202: Theme 3, Modulatory systems in psychiatry > Neurobiology and neurochemistry or reward based behaviours > Flashcards

Flashcards in Neurobiology and neurochemistry or reward based behaviours Deck (32)
Loading flashcards...
1

Addiction

Persistent disorder of brain function where compulsive drug use occurs despite serious negative consequences in afflicted individual
- Due to changes in synaptic plasticity

2

Withdrawal symptoms

Negative physiological and emotional features that occurs when a drug is not taken.

Usually opposite to positive experience induced by the drug

3

Tolerance

Diminished response to the effects of a given amount of drug
- Due to repeated exposure to the drug

Increasing larger dosage is required to have the same effect

4

Regions in the brain for the natural reward system/ addicition

Mesocorticolimbic system

Prefrontal cortex

Amygdala

Hippocampus

5

Dopamine error / learning signal

When given a reward with no stimulus
- There is a spike in activity after the reward

When given a stimulus prior to the reward
- Spike in activity before reward
- Anticipation of the reward is more pleasurable than receiving the reward

When reward does not come
- Anticipation still spikes
- Fall in dopaminergic effect

6

Predicted vs unpredicted stimulus and learning

Unpredicted reward = increased activity in nucleus accumbens
- Tells the brain they should be something being learned

Predictable = response in temporal lobe
- Indicates learning has taken place

7

Functions of the Reinforcement System

Detect reinforcing stimulus
- Recognise something good has just happened
- Time to learn

Strengthen neural connections
- Between neurons that detect the stimulus and the neurons that produce the instrumental response
- Long term potentiation

8

Natural reinforcers for reward

Food
Sex

Causes extracellular dopamine release in nucleus accumbens

9

Psychostimulants
- Effects on dopaminergic system

Directly affects dopaminergic neurones in the nucleus accumbens

10

Opiates
- Effects on dopaminergic system

Indirectly – inhibit GABAergic interneurons in VTA
- Disinhibition of VTA DA neurons

11

Alcohol
- Effects on dopaminergic system

Disinhibition of dopamine neurones

12

Nicotine
- Action

Increases Nacc DA directly and indirectly

Stimulates nicotinic cholinergic receptors on mesocortiolimbic DA neurons

13

Dependance

Homeostatic response to repeated drug administration

Unmasked by withdrawal

14

Sensitisation

Repeated administrating of drug = escalating effects

15

Cocaine and amphetamine
- Mechanism
- Role in reinforcement

Inhibits dopamine, serotonin and noradrenaline reuptake transporters
- Cocaine inhibits
- Amphetamine reverses transporters

= Increased synaptic DA

Reinforcement
- Action on dopamine transporter on plasma membrane

16

Cocaine and amphetamine
- Effects

Psychosis

Long term
- Decreases dopamine transporters and terminals
- Increased cellular and molecular changes that promote dysregulation

Hypofrontality [decreased blood flow to prefrontal cortex]

17

Increased excitatory strength and drug abuse

Drug abuse shows significant increase in AMPA/NMDA ratio

= Increased basal excitatory synaptic strength

18

Dopamine receptors in addiction

Fewer D2 receptors
- Reduces sensitivity to natural rewards that develops with addicition

19

Molecular activity of emotional dependence

Compensatory changes in the VTA or Nucleus accumbens = lower DA transmission

At first;
- Increased D1 receptor activity in NAcc sets off Gs protein signalling

PKA and cAMP release =

VTA
- dynorphin synthesis and release is inhibited
- Acts on K opiod receptor

Nucleus accumbens
- Less DA release

20

Associative learning and addiction

Coincident firing in sensory and mesocorticolimbic pathways
= LTP induction = strengthened synaptic connections

Glutaminergic synapses form on reciprocal connections in:
- NAcc
- VTA
- Cortex
- Hippocampus
- Amygdala
= Potential sites for LTP

Information present at the time of drug induced DA release -----> associated with drug taking

21

Dopamine and LTP

DA acts on D1 receptor [Gs protein]
- Increase in PKA = gulatamatergic transmssion = LTP

Late phase LTP
- CREB protein mediation and protein synthesis

Synaptic remodelling
- Increased spines and dendrite branches
- long term molecular and
cellular changes remain
months after abstinence
- Memories in these
pathways may trigger
relapse years later

22

Opiates
- Action
- Reward and reinforcement

Acts on endogenous opioid receptors (Gi coupled)

Morphine mainly acts on gamma receptors

Reward and reinforcement
- Disinhibition of DA neurons in VTA

- Action at opiate receptors in the NAcc - independent of DA release (μ or δ)

23

Alcohol
- Mechanisms

1. GABA-alpha agonist

2. NMDA antagonist
- In the VTA cortical inputs = disinhibits VTA DA neurones
- Increases Dopamine release in the nucleus accumbens

Rewarding effects blocked by DA receptor antagonists in NAcc

24

Naltrexone and alcohol

Opiate antagonist
- Reduces alcohol self administration in animals

- Used to reduce alcohol consumption, relapse and craving

25

Nicotine
- Mechanism

Acts on nicotinic Ach receptors

Nicotine = release of dopamine in nucleus accumbens due to:
- Activation of receptors on cell body in the VTA
- Facilitated DA release by pre-synaptic receptors in NAcc

26

Opiates and nicotine

Opiates block nicotine induced behaviours and self administration
- I.e Naltrexone used to add smoking cessation

27

Physical dependancy on opiates

Locus coeruleus
- Contains opiate receptors
- Nucleus involved in attention, arousal and vigilance [NADR]

Chronic activation of opiate receptors = homeostatic compensation = tolerance and physical dependance

28

Morphine and locus coeruleus

Acute morphine = inhibits LC neurones

Chronic morphine = LC neurones return to firing state

Withdrawal = Dramatic increase in LC neurones firing
- Over activation of ANS

29

Clonidine

Alpha-2 agonist that blocks the over activation of ANS seen in physical withdrawal of opiates

30

Physical dependance to alcohol

Acute effects
- GABA-alpha agonist
- NMDA antagonist
= Cell firing inhibited

Chronic
- Downregulation of GABA-alpha
- Upregulation of NMDA
- Firing rates normal in presence of alcohol

Withdrawal
- In alcohol absence= excitation
- Physical symptoms