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Chapter 14 - Psychological Disorders

Terms in this set (37)

Once addictive behavior is learned, presenting the environmental cues that have been previously associated with drug intake can cause a conditioned or learned dopamine release in the nucleus accumbens
- environmental context and stimulus cues can elicit a learned conditioned dopamine release
- stimulus elicited is directly associated with cravings and can produce relapse

In mice, a tone is repeatedly paired with cocaine
- during a test, present the tone and measure the nucleus accumbens dopamine release
- a control group who hasn't has cocaine paired with tone, there's no change in dopamine release
- when conditioned, there's a dramatic dopamine release upon tone

A second experiment sought to drive this relationship
- people who were cocaine addicts watched either a video that was neutral or a drug video (cocaine associated cues)
- measured the binding of a particular dopamine antagonist
- ralcopride (if dopamine is released in the brain there will be fewer binding sites available for a drug that binds to dopamine receptors)

Ralcopride binding was much less in people who watched the drug video
- when cocaine addicts watched the cocaine video and rated how much they craved cocaine, the relationships was that the stronger the cue induced dopamine release, the stronger the cravings

Cue-induced dopamine release produces cravings
- anti-drug campaigns (older ones would show images of the darker side of addiction (drug cues)
- could promote drug relapse (now they focus on the skin, hair, teeth, health things, social effects, etc.
Opiates (heroin, morphine, methadone, codeine)
- enhance mood and can be strong analgesics
- heroine is very addictive and is unique because it is fat soluble and can rapidly cross the blood-brain barrier
○ strong and immediate flood of receptor stimulation, stronger and faster high

Gaba neuron inhibits (projects onto) a dopamine neuron
- if dopamine neuron fires, dopamine will be released and its normal job is to inhibit the release
- opiate rugs will bind to receptors on the presynaptic terminal bouton on the gaba neuron and inhibit the gaba neuron so that the gaba neuron does not inhibit the dopamine neuron
○ dopamine is released
○ indirect

Methadone doesn't cross the blood brain barrier as quickly as heroine, thus lowering the dosage
- addicts receiving methadone treatment (pill) would break the pill apart and shoot it to get a better high
- they started adding naloxone to the methadone pill (an opiate antagonist)
○ stomach enzymes quickly metabolize naloxone
○ if an addict broke apart the methadone pill that contained naloxone, the naloxone would block the dopamine receptors and they wouldn't get high

Marijuana/cannabis sativa
- THC is sometimes medically prescribed for different conditions used to treat pain and nausea
- thought to affect time perception
○ there are endogenous chemicals in the brain that bind to cannabinoid receptors
○ can affect memory and motor function
- Overdose is relatively unlikely because there aren't many cannabinoid receptors in the brainstem
- there are 2 endogenous chemicals that bind to those receptors
○ anandamide (retrograde transmitter - released by the post-synaptic neuron but travels backward to affect the presynaptic cell)
○ 2-ag
○ both inhibit neurotransmitter release
○ people don't know what there chemicals are
Distinguishes between wanting the drug (motivational process, incentive-salience) between liking the drug (makes you feel good, hedonic/pleasure reaction)

Incentive sensitization theory argues that wanting and liking are independent systems
- key feature is that neural systems become overactive and sensitized and that these systems mediate change sin liking

The neural systems for wanting and liking can be sensitizes, but the neural systems responsible for wanting go into overdrive (pathological motivation to take the drug independent from wanting)

Increase in inceptive salience to take the drug

Stimulus induced dopamine release - increased salience for drug associated cues

Dopamine hypothesis of addiction is that drugs of abuse cause a big dopamine release that makes it feel really good and this is strongly reinforcing and rewarding

Incentive salience theory says that dopamine plays a critical role in
addiction but not because it makes you feel good.

Origins in the idea that dopamine itself is involved with reward and reinforcement
- animals dopamine-deficient will cause animals to stop eating and drinking but can be reversed with dopamine agonists or precursors (critical role in reinforcement)
○ dopamine reward hypothesis says they stop eating because food is no longer pleasurable
○ incentive sensitization hypothesis says that the animals are still capable of pleasure but they are no longer motivated to eat (no wanting, but capable of liking)

Hedonic reaction to taste reactivity tests (I like it responses)
- arguing dopamine is not responsible for liking
○ large lesions that reduce dopamine transmission in the brain do not change the hedonic reactions
- arguing dopamine is reponsbile
○ when amphetamine that enhances dopamine at the synapse is administered to animals, more dopamine causes the rats to work harder and pushes a level more
○ with increased dopamine release the animals work harder for sucrose even there's no change to the hedonic responses
○ Liking and how much you're willing to work for it are independent

Where is pleasure?

Opioid system - in the nucleus accumbens they have discovered "hedonic hotspots" where there are densely populated opiate receptors
- finding that opiate agonists dramatically increase the hedonic liking responses to sucrose

Opiate agonists increase pleasure at these hotspots

The progress of addiction
- initial drug takin g behavior is produced because someone stimulates opiate receptors that makes drugs taking fell good
- what causes progression to addictive dependence is sensitization of motivational wanting
The rise of these neurotransmitter hypotheses of depression gave rise to pharmacological therapeutics

MAO inhibitors block the action of monoaminoxidase and therefore block the breakdown of monoamines in the presynaptic terminal (more transmitter available for release)
- First used as an ingredient in rocket fuel, and then started to be used as a treatment for tuberculosis and their antidepressant features were discovered
- There are a lot of contra-indications, including food interactions

Cheese effect is cardiovascular hypotension
- Tyramine is an amino acid that is normally broken down by MAO
- High levels are bad
- When someone takes an MAO inhibitor, tyramine is not broken down
- Given a dietary list to eliminate consumption of certain foods hugh in tyramine

Tricyclics block the reuptake of monoamines (imipramine)
- if you block reuptake, the transmitter will last longer in the synapse
- Can be effective in alleviating depressive systems, but can also produce a depression-like state called dysphoria in someone who is not depressed

SSRIs block reuptake of serotonin
- well recognized drug is prozac
- lasts longer at the synapse, which leads to more post synaptic activity

- if someone is regularly taking a drug, the receptor bed is used to getting binding, but when they quit there is functional depletion of the neurotransmitter at the synapse
○ the functional depletion is associated with withdrawal and relapse
○ drugs like his can help people stop their addictive habit by minimizing negative effect of withdrawal
Schizophrenia is known as dementia praecox (premature deterioration of the mind)
- used to be though of as a spilt mind disease (not multiple personalities)
- split is between affect and cognition

Affect alterations are inappropriate emotional responses

Cognition effects are thought disorders and illogical thinking

Symptoms are positive and negative systems
- positive - present but shouldn't be
○ hallucinations and delusions
○ more sporadic
- negative - absent but should be there
○ emotional stoicism
○ tend to be more stable

When a schizophrenic is having a depressive episode, they are most likely truly seeing and/or hearing these things
- increase in neural activity suggesting they are not making it up, but the brain is releasing something that is not physically present

Both genetic and environmental hypothesis and influences

genetic concordance rate in identical twin studies

environmental hypotheses
- neurodevelopment hypothesis: there's some alteration in normal neural development early on that later becomes manifested as schizophrenia
○ season of birth effect where more schizophrenics are born in late winter or early spring (second trimester is in the fall - flu season, fetus could be exposed to virus)
○ the virus itself might not cross the placental barriers, but cytokines do (proteins elevated when immune system is engaged)
§ do an can impair brain development
§ temperature goes up, causing subtle alterations in the developing nervous system that become manifested as schizophrenia
§ incidence of schizophrenia is tropical parts of the world tend to be lower with no real flue season
neurological correlated
- when we scan a visual scene, our eyes make saccadic movements (don't move continuously)
○ normally jumpy psychotic movements tend to not smooth out in a schizophrenic
- key cognitive features is attentional dysfunction, irregularity might reflect a neurological correlate in neurological deficits

He number of manic episodes in correlated to the size of the ventricles

The length the person has been diagnosed is not correlated to ventricle size, but how effective medication will be is negatively correlate to ventricle size
- larger the ventricles, the less the positive response to medical treatment

The number of manic episodes in correlated to the size of the ventricles

The length the person has been diagnosed is not correlated to ventricle size, but how effective medication will be is negative3ly correlate to ventricle size
- larger the ventricles, the less the positive response to medical treatment

There was a large Scottish family discovered where several members had schizophrenia
- researchers gravitated toward this family to study the disease genetically
- DISC1 gene
○ regulates spinal glutamate synapse
- mouse model was developed that had the same gene disables
○ led to enlarged ventricles just like the schizophrenic brain

Also like bipolar, gray model loss is also associated with schizophrenia
- gray matter loss is developmentally regulated (tends to be accelerated in adolescence)

Other brain abnormalities are reduction in frontal cortex activity (hypofrontality hypothesis)
- at rest, if you measure baseline frontal cortex activity, there is less activity in non-schizophrenics than schizophrenics
- if you asks someone to engage in a task that would require engagement of the frontal cortex, there is less of an increase of PFC activity in schizophrenics than non schizophrenics
Transmitter hypotheses
- dopamine theory of schizophrenia (too much dopamine in the schizophrenic brain)
○ drugs that increase dopamine in the brain can induce psychotic-like symptoms of schizophrenia
§ amphetamine psychosis (promote the release of dopamine)
§ L-dopa is a precursor to dopamine and is a treatment of Parkinson's (often develop psychotic symptoms)
○ drugs that decrease dopamine can decrease schizophrenic symptoms
§ dopamine antagonists

2 major classes (dopamine antagonists that target different dopamine pathways)
- typical antipsychotics (chlorpromazine)
- atypical (clozapine)

Textbook has a section on the mesolimbocortical pathway

typical anti-psychotics are most effective at treating positive symptoms
- expresed through abnormalities in the mesolimbic area (VTA-NA)

atypical antipsychtic are mot effective in treating negative symtpoms (mesocortical pthway midbrain to cortex)
- thinking and cognition

nigrastriatal pathway supplies dopamine to the basal ganglia

side effects of these medication is that is can produce side effects that don't go away
- tardive dyskinesia
- extra-pyramidal syndrom
- (involuntary movements)

Second generation anti-psychotic drugs reduce the risk of ardive dyskinesia

EXAM ALERT: Know each drug class, symtpoms, pathway

- effective neuroleptice do activate dopamine receptors
- if a schizophrenic takes amphetamine (causes dopamine release) it tends to cause a larger dopamine release

- dopamine metabolite levels don't always differ in schizophrenic and non schizophrenic populations
- anti-psychotics don't work right away even through they upregulat the availability of dopamine at the synapse immediately

- different classes of medications that affet positive and negtive symtpoms (not just too muchdopamine)
- dopaine antagonists don't only affect the sopamine system
○ serotonin
○ glutamine transmission