Term
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Definition
| A form of neuroplasticity where maladaptive learning occurs. It is the dysregulation of reward and stress mechanisms, as well as anatomical changes in the brain. |
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Term
| Name the psychostimulants: |
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Definition
| Nicotine, cocaine, caffeine, amphetamine |
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Term
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Definition
| Mescaline, LSD, PCP (hallucinogens), marijuania |
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Term
| Name the Sedative Hypnotics: |
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Definition
| Depressants: alcohol, barbiturates, sleeping pills, inhalants |
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Term
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Definition
| Opiates: morphine, codeine, heroin, methadone |
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Term
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Definition
Physical Dependence: Withdrawal
Psychological dependence: Cravings
Tolerance: Metabolic & Cellular |
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Term
| What is the difference between metabolic and cellular drug tolerance? |
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Definition
Metabolic: drugs are broken down with Cyt450 enzymes in the liver, upregulation of these enzymes causes the drug to be broken down more quickly.
Cellular: Receptor affinity can change over time due to cell protein expression. This causes weak binding and thus the need for higher drug concentrations in order to achieve the same effect. |
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Term
| What are the differences between positive, negative and conditioned reinforcement? |
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Definition
Positive: drug makes you feel good, so you want to take more.
Negative: Drug makes you feel bad when you don't take it, so you want to take more.
Conditioned: you get addicted to activities associated with the drug due to conditioning (ex: smoking after sex). |
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Term
| What properties make up the potential for drug abuse? |
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Definition
Withdrawal
Reinforcement
Tolerance
Dependence
Intoxication |
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Term
| What is the criteria for drug abuse? |
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Definition
12 months of 1 or more of:
1. Failure to fulfill major role obligations,
2. Use of a substance when it is physically hazardous.
3. Legal problems associated with the drug.
4. Generating social or interpersonal problems due to drug use. |
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Term
| What is the criteria of drug addiction? |
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Definition
3 or more of the following in 12 months:
1. Tolerance
2. Withdrawal
3. Craving |
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Term
| What is the addiction cycle? |
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Definition
| It is the progressive dysregulation of the brain reward system where larger amounts of drug are taken, there is positive reinforcement, then there is withdrawl that negatively reinforces taking the drug and finally the conditioned reinforcement causes the individual to take more of the drug. |
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Term
| Briefly describe the components of a homeostatic negative feedback loop: |
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Definition
1. Set point becomes unbalanced
2. Detector senses imbalance
3. Correctional system engages to correct imbalance.
4. System variable is acquired and imbalance is corrected.
5. Detector senses correction in imbalance and shuts off the system. |
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Term
| Briefly describe the components of an allostatic feedback loop: |
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Definition
| The absence of a homeostatic system regulator causes the system to acquire the drug that ultimately causes the need for more drug. There is no negative feedback in the loop. |
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Term
| What are the factors that affect addiction? |
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Definition
| Biological, Psychological and sociocultural |
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Term
| How can we increase dopamine release in the brain? |
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Definition
1. Directly: increase activity in the VTA
2. Indirectly: stop GABA transmission to the VTA and from the NAc. |
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Term
| What is dynorphin and how does it work? |
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Definition
| Dynorphin is activated through the PKA pathway upon DA binding in the NAc. Dynorphin then is released onto the VTA DA sending neuron to act as a feedback inhibitor. |
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Term
| What is the HPA stress system? |
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Definition
| Hypothalamic-pituitary-adrenal brain stress system: Pituitary releases ACTH in response to stress, this causes the adrenal medulla to release glucocorticoids which act on many parts of the brain, including the amygdala. |
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Term
| How do drugs change the reward systems? |
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Definition
| In non-dependent users, the VTA-NAc circuit dominates the positive reinforcement behaviors. In dependent users, negative reinforcement dominates because of increases in NE-CRF from the amygdala. |
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Term
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Definition
| Orexin is a NTM that is released from the lateral hypothalamus. It causes the increase of AMPA and NMDA receptors, ultimately causing an increase in glutamate signaling strength. This acts on the VTA and contributes to addiction associated behaviors. |
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Term
| Where does dopamine come from? |
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Definition
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Term
| What is the difference (NTM-wise) between a normal drug circuit and an addicted circuit? |
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Definition
| The normal drug circuit causes DA release. The addicted circuit is seeking drugs and causes a glutamate release. |
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Term
| Why are drug changes considered maladaptive learning (concerning memory)? |
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Definition
| The NAc deals heavily with kinds of memories and also their eventual behavioral output. This any changes in the NAc can cause maladaptive learning. |
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Term
| What is the integration of addiction? |
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Definition
| Changes over control, saliency, memory and motivation in the brain shift behavior. |
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Term
| How does the ERK pathway influence addiction? |
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Definition
| The ERK pathway deals with plasticity of signals. |
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Term
| How can drugs influence changes in the nucleus that affect addiction? |
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Definition
| Histone modifications mediate some of the changes involved in addiction. |
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Term
| In what ways do cellular modifications affect addiction? |
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Definition
1. Plasticy changes within MEK signaling
2. Histone Modifications
3. Cytoskeletal reorganization |
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Term
| How is addiction integrated? |
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Definition
1. Nucleus accumbens- translate motivation into action.
2. Dorsal striatum- learn how to get reward efficiently
3. Orbital Prefrontal Cortex- representations of rewards
4. Prefrontal cortex- goal-driven behaviors
5. Forebrain/brainstem: leaning of behaviors |
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Term
| What are psychostimulants? |
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Definition
| Psychoactive drugs that increase alertness, heighten arousal, cause psychomotor activation. (increase brain metabolic and neural activity) They affect the mesolimbic system, the basal ganglia and ARAS. |
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Term
| What type of NTMs do psychostimulants affect? |
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Definition
| Modulatory NTMs including the monoamines and acetylcholine. |
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Term
| What is the anatomy of the dopaminergic system? |
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Definition
80% of CA
Originate in the substantia nigra, VTA and Arcuate Nucleus. |
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Term
| What is the anatomy of the noradrenergic system? |
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Definition
| The fibers originate in the brain stem in the locus coeruleus, lateral tegmental and dorsal medullary regions. There are less much fewer than the DA system. They affect the sympathetic ANS with arousal and also eating behaviors. |
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Term
| What is the CA hypothesis? |
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Definition
DA system: provides incentive to approach reinforcing stimuli.
NE system: Facilitates learning and attention during the behavior. |
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Term
| What is so special about CA synthesis? |
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Definition
| CA are limited by the enzyme tyrosine hydroxylase. The steps are also sequential in the formation of dopamine, norepinepherine and epinepherine. |
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Term
| Where is dopamine made? Where is NE and EPI made? |
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Definition
| Dopamine is made in the cytoplasm and is actively broken down by MAO (monoamine oxidase). NE and EPI are made in dense core vessicles and dopamine must be transported into them via VMAT receptors in order for production to be successful. |
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Term
| What about the catechoaminergic receptors? |
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Definition
| Theyre all GPCRs and there isnt an epinepherine receptor. It actually binds to noradrenaline receptors. |
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Term
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Definition
| The D2 receptor is an important dopamine autoreceptor. These are often found in the NAc. |
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Term
| Where are the beta adrenergic receptors located? |
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Definition
| The heart as well as other ANS locations. This is why beta blockers are used. They can slow down heart rate and force of contraction. |
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Term
| How is dopamine inactivated? |
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Definition
| It is taken back up into the cell where it is broken down by either MAO or COMT (need both) to eventually yield homovanillic acid (HVA). |
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Term
| How is the NE system inactivated? |
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Definition
| It is taken back up by the cell where either MAO or COMT break it down to a variety of end products. MAOa breaks down NE and DA where MAOb breaks down 5-HT and histamine. |
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Term
| What is the anatomy of the serotonergic system? |
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Definition
| The serotonergic system is more spread out with 90% of it within the PNS. The largest portion in the CNS is within the nucleus raphe within the brain stem. |
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Term
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Definition
| It acts as a behavioral suppressant and also has many affects on the PNS. |
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Term
| How is 5-HT synthesized? How is it regulated? |
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Definition
| 5-HT is limited by the amount of tryptophan (not the tryptophan hydroxylase enzyme). It is produced in the cytosol. Its synthesis is regulated by neural activity and also competition between other amino acids that try to cross the blood brain barrier. |
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Term
| What is the 5-HT receptor? |
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Definition
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Term
| How is seretonin inactivated? |
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Definition
| MAOb breaks down seretonin (and histamine) after reuptake. |
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Term
| What is the anatomy of histamine? |
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Definition
| Projections originate from the tuberomammillary nucleus. It regulates lots of things like sleeping/waking/energy/learning. |
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Term
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Definition
| Histidine is decarboxylated and histamine can then be made into other products/ broken down. |
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Term
| What factors affected the abuse of behavioral stimulants throughout history? |
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Definition
availability,
price,
socio-cultural norms |
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Term
| What are the pharmacokinetics of cocaine? |
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Definition
| Peak absorption within 30-90 minutes, cholinesterases (hepatic mixed oxidases) affect the amount absorbed + breakdown (usually takes between 2 days and 2 weeks to eliminate). Alcohol added to cocaine produces cocoethylene (which has a half life of approximately 150 minutes). |
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Term
| What are the pharmacodynamics of cocaine? |
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Definition
| It reversibly blocks sodium channels (as in the case of novicane) and acts as a vasoconstrictor (floppy dick). It also prevents the reuptake of dopamine by blocking the transporters. |
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Term
| What are the pharmacodynamics of cocaine? |
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Definition
| It reversibly blocks sodium channels (as in the case of novicane) and acts as a vasoconstrictor (floppy dick). It also prevents the reuptake of DA, NE and 5-HT by blocking the transporters. This causes adversive effects for the NET, but not DAT or SERT. |
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Term
| What are the long term effects of cocaine? |
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Definition
1. acetylation of histones
2. lower dopamine binding
3. Changes in dendrites, laminar positioning, cell outgrowths and GABA migration, etc...
4. Bermuda square of neuroadaptations. |
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Term
| What are the pharmacokinetics of the amphetamines? |
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Definition
| They are usually oral, smoked or snorted. They aren't easily absorbed in the stomach because they have a pKa of 9.9. They have an onset of 30 min for a duration of 4-6 hours. It is slowly broken down by the liver over up to 3 days. |
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Term
| What are the pharmacodynamics of amphetamine? |
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Definition
| It causes the spontaneous nonvesicular release of monoamines. It also causes changes in membrane trafficking and a change in the AMPH transporter. |
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Term
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Definition
| It is a MAO inhibitor. It is not a clean drug since MAO enzymes catalyze the breakdown of all of the monoamines. It is a tricyclic antidepressant. |
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Term
| What is the difference between mania and depression when we talk about NTMs? |
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Definition
| Depression is the decrease in monoamines whereas mania is the increase in monoamines. |
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Term
| How can we test the stress neuroendocrine system? |
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Definition
| Administer dexamethasone (inhibits glucocorticoid release) and see levels in blood. |
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Term
| What is the neuroplasticity and cellular resilience impairment? |
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Definition
| NCR is the cellular response to decreased levels of 5-HT, NE, increases in cortisol and glutamate and decreases in BDNF. |
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Term
| What are the circuits of the NCR? |
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Definition
| The hippocampus and the amygdala have a push and pull relationship with the hypothalamus and the eventual cortisol release. An increase in cortisol decreases VEGF and decreases neurogenesis. |
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