Addiction

Question 1

Natural reinforces

Answer 1

Natural reinforcers (e.g. food and sex) increase
extracellular Dopamine in the Nucleus Accumbens

(dopamine levels measured by microdialysis)
All known addictive drugs also activate this system

Behaviours leading to activation tend to be repeated (are reinforced)

Blockade of DA in this region attenuates most measurable reinforcing and rewarding effects of addictive drugs

Question 2

Mechanisms by which addictive drugs increase dopamine availability/release in Nucleus accumbens (NAcc)

Answer 2

Direct:

Cocaine / amphetamine - increase availability at synapse by blocking or reversing dopamine transporters

Nicotine - direct excitation of VTA neurons by action at nicotinic receptors

Indirect:

Opioids / Cannabinoids - action at opioid or cannabinoid receptors indirectly leads to modulation of VTA activity

Question 3

Associative Learning

Answer 3

“cells that fire together wire together”

Sensory information - people, places, emotions etc present at the time when DA release occurs will become associated with reward

Reward associated cues will trigger reward seeking behaviour

e.g. Go into bakery and buy cake
“Crave” a cigarette when you go into a pub etc.

Question 4

Associative Learning - what makes drugs addictive?

Answer 4

Coincident firing in NAcc will induce LTP, strengthening synaptic connections

 - Sensory inputs (Glutamate) from cortex, hippocampus,  amygdala	
 - Dopaminergic inputs from VTA

Drugs of abuse – direct activation of DA circuitry

 powerful reinforcers - hijack the system

Question 5

Frontal system dysfunction in chronic substance abuse

Answer 5

Hypofrontality - their frontal cortex doesn’t light up as much in the addicted brain

People who have less activity in the dorsal frontal cortex they are more susceptible to wanting drugs

Question 6

Frontal system dysfunction in chronic substance abuse

Answer 6

Damage to the nucleus accumbens decreases self-administration of heroin.

Mesocorticolimbic pathway needed for drug to have a rewarding effect.

Question 7

Psychomotor stimulants

Answer 7

Cocaine and amphetamine. Cocaine blocks and inhibits transporter to prolong pool of extracellular DA. Amphetamine reverses transporter to increase extracellular DA levels

Question 8

Opiates (e.g. morphine and heroin)

Answer 8

Act at endogenous opioid receptors (Gi/Go coupled)
Inhibitory - decrease adenylyl cyclase activity
- lead to open K+ channels, closed Na+ channels

Different subtypes on different cells in different brain regions (μ, κ, δ). Most of morphine’s analgesic and rewarding properties are through actions at μ (mu) receptors

Subjective effects:
Euphoria and intense rush with heroin compared to morphine due to route of administration and entry to brain (seconds vs minutes)
Relaxing effects – inhibition of Noradrenergic pathways
Physical dependence – compensatory changes in these pathways

Question 9

Alcohol (EtOH)

Answer 9

Subjective effects of EtOH
Low doses of alcohol - mild euphoria and anxiolytic effects
Higher doses - poor coordination, amnesia, sedation
Chronic alcoholism - Korsakoff’s Amnesia
Damages the cerebellum which is why you have poor coordination.

Question 10

Nicotine

Answer 10

ction at nicotinic acetylcholine receptors (nAChRs)

-Ligand gated ion channels located pre or post-synaptically
(present throughout brain, excitatory or modulatory)

-Presynaptic receptors - influx of Ca2+ - transmitter release

Unlike cocaine and opiates - powerfully reinforcing in absence of subjective euphoria

Question 11

Opiate dependence

Answer 11

Chronic activation of opiate receptors leads to homeostatic mechanism that compensates for the functional changes leading to tolerance and physical dependenceAcute morphine - acutely inhibits firing of LC neurons through Gi pathway
Chronic morphine - LC neurons return to their normal firing rates
(Gs pathway component upregulate to match Gi)
Withdrawal - dramatic increase in LC firing
(In absence of Gi inhibiton Gs hypersensitive)