PBSI 336: Exam #2

What are the main structures of the Brainstem ?

Midbrain , pons, & medulla

What are the major striatum components?

Nucleus Accumbens , caudate (Dorsomedial striatum), and putamen (Dorsolateral Striatum)

What is the Nucleus Accumbens associated with?

Pleasure, Motivation, & Reward Cues

What is the Dousomedial Striatum associated with ?

Goal - Directed Actions

What behaviors are associated with the Dorsolateral Striatum?

Habits

What is the major target for dopamine (DA) axon terminals in the brain?

Striatum

Are there DA neurons in the striatum ?

No

Where are the cell bodies for DA neurons located?

Brainstem

What parts of DA are located in the striatum ?

DA fibers, DA release at synapses, & DA receptors/transporters

What are the monoamine neurons ?

Dopamine, Serotonin, & Norepinephrine

where are monoamine neurons located?

Primarily in the Brainstem

Where do monoamine neurons send axon projections?

Throughout the brain

where are the majority of dopamine neurons (cell bodies) located in ?

Substansia Nigra & Ventral Tegumental Area (VTA)

What is the source and target of axons for the Nigrostriatal Pathway ?

source is DA neurons in substansia nigra; target of axons is dorsal striatum

What is the source and target of axons for the mesolimbic pathway?

Source is DA neurons in the VTA; Target of axons is nucleus accumbens and amygdala

What is the source and target of axons for the mesocortical Pathway?

Source is DA neurons in VTA; Target of axons is prefrontal cortex

What are the limbic areas?

Moods, emotions, & rewards

What are Basal Ganglia circuits important for ?

voluntary movement, action selection, procedural learning, habits

What are the major Input structures ?

Cortex; Glutamatergic (excitatory)

What are the major output structures?

GPI & SNr; GABAergic (inhibitory)

Where do striatum projections (GABAergic go?

Directly to Output Structures (GPi , SNr) or indirectly (GPe , STN)

What does the Direct Pathway do?

Excites targets of BG output (GO)

What does the indirect pathway do ?

Inhibits targets of BG output (No-go)

What provides feedback in the system and complete the loops?

Midbrain dopamine & thalamus

In the striatum, GABA neurons express what two receptors?

Dopamine DI receptos (Gs) & D2 Receptor (Gi)

Which Pathway are D1 neurons apart of and what does Dopamine do ?

Direct ("Go"); activated

Which Pathway are D2 neurons apart of and what does Dopamine do ?

Indirect ("no-go"); inhibited

Do all addictive drugs have the same property of increasing dopamine?

yes, but it is via different mechanisms

What are the components of reward learning?

Liking, Wanting, Reward prediction

What is liking, does it involve DA?

Affective/hedonic/pleasurable aspects (Does NOT involve DA)

What is wanting, does it involve DA?

Motivational/Incentive/drive to Obtain reward (Involves DA)

What is reward prediction, does it involve DA?

Learning about "cues" related to reward (Involves DA)

Does liking involve Dopamine ?

No (does involve endogenous opoiods and cannabinoids in NaCC)

Does wanting involve dopamine?

Yes

What shows a temp. Increase in firing rate when a reward is given unexpectedly?

Dopamine Neurons

After training, when do DA neurons show increased firing?

when the CS is presented rather than the reward

Reward Prediction Error

if reward is omitted , a decrease in DA neuron firing is observed

What does positive Prediction Error activate ?

D1 cells (G, coupled) and Direct Pathway

What does Negative Prediction Error Activate ?

D2 cells (Gi coupled) and Indirect Pathway

positive Prediction Error

more activity with unexpected reward

zero Prediction Error

same activity for predicted reward

Negative Prediction Error

less activity with loss of reward

What are the teaching signals for learning about rewards?

Dopamine

What are the factors that cause Addiction?

Properties of drugs, Individual differences (genetic & environmental), and Drug Induced Neuroadaptations

What factors influence Addiction Vulnerability?

Properties of Drugs, Individual Differences, and Drug-Induced Neuroadaptations

What are the Individual Differences?

High Impulsivity, History of Stress, and Environmental Enrichment

What do the Drug-Induced Neuroadaptations cause?

Enhanced Drug Motivation , Enhanced Habit Learning, and Reduced Behavioral Inhibition

What are two traits of Addiction?

Compulsive Seeking of Drugs & Craving/Relapse

What does Route of Administration affect?

(speed of Onset) Addiction Potential

What does Increased Lipid Solubility do?

Allows drug to reach brain faster (ex: heroin IV vs . Morphine)

What part to genes play in Addiction ?

Contribution to Vulnerability's Resilience (ex: genes for metabolic enzymes , receptor #/signaling, Stress response)

Explain gene x environment interaction

Complex interaction of genes and environment for increased likelihood of addiction

What are some genetic/enviormental factors that affect Addiction likelihood ?

High Impulsivity, Enhanced habit learning, & Reduced Behavioral Inhibition

Do High Impulsivity Rats administer more or less cocaine what does this indicate?

More; Impulsivity may be a pre-existing condition for addiction

What aspects of the Addiction process does stress effect?

All; initial drug taking, reward, vulnerability to addiction, & relapse

which rats showed greater/reduced CPP for low-dose cocaine ?

Rats w/history of social defeat vs Rats w/ environmental enrichment

What is the Prefrontal Cortex (PFC) involved in?

Behavioral Inhibition, Self-control, executive function, Resolving conflict in behaviors

What is the Nucleus Accumbens (ventral striatum) involved in?

Reward, motivation, and cues

What is the Dorsomedial striatum (DMS) involved in?

Goal - Directed Learning; flexible, rapidly acquired

What is the Dorsolateral Striatum (DLS) involved in?

Habit Learning; Automatic, inflexible

Habit vs. Goal-Directed

Stimulus - response association vs. response - outcome association

What does chronic stress cause?

enhanced habit learning (insensitivity to out come devaluation), loss of PFC volume, & reduced dendritic complexity, and changes in neural density (DLS becomes more dominant)

What are some drug factors that increase Addiction likelihood

sensitization of drug effects, Enhanced habit learning, & reduced behavioral inhibition

What does the Animal Self-Administration Model w/ Intermittent cocaine use show ?

Sensitization of DA system , increased cocaine potency, & Increased Drug Motivation

What do Rats become Resistant to on Self-Administered cocaine?

Punishment; foot shocks & food removal

What does Optogenetic Stimulation/Inhibition of PFC do?

Restores sensitivity to foot-shock (stimulation); makes animals resistant to foot shock (inhibition)

What "larger class" of drugs do Cocaine & Amphetamines belong to?

Stimulants, Psychomotor stimulants, psycho stimulants , or "uppers*

What are the major behavior properties of psychomotor stimulants ?

Stimulate Alertness/Arousal & stimulate motor activity

What are the four stimulants?

amphetamines, cocaine, nicotine, caffeine

What is the natural form of cocaine?

Psychoactive Alkaloid found in coca leaves (in South America)

Is cocaine a strong or weak base?

Weak

In the early 1800s how was cocaine used?

widely used; Drs and scientists saw a lot of potential in its properties

W hat is the Route of Administration for coca leaves ?

Raw coca leaves are chewed with lime/ash to increase Saliva PH , (increases absorption by lowering ionization) sublingual; concentration is <2 % cocaine

What is coca paste?

Crude extraction from coca leaves mixed w/ sulfuric acid

What is the Route of Administration of Coca pastes concentration ?

can only be smoked; 80% cocaine sulfate

What is "Paco" ("basuco") ?

cheap , low grade cocaine ; abused in low income areas of south America

What is Cocaine HCL?

Crystalline powder purified from coca paste

What is the Route of Administrations & Concentration of Cocaine HCL?

orally, intranasally, o r injected IV . (Water soluble); Can NOT be smoked b/c vaporization tmp & burn temp are too close

What is cocaine free base?

made from cocaine, HCL, base (ex: ammonia) extracted w/ether (flammable solvent)

What is the Route of Administration of cocaine free base?

vaporized or smoked ("freebasing"); caveat is ether can explode with flame

What is crack cocaine?

"Cruder" version of free base (made from Cocaine HCL); safer b/c made w/baking Soda (not solvent)

What is the Route of Administrations & Concentration of Crack ?

Smoked; 75-90%

What did crack cause in the 80s/90s?

A "new" epidemic of cocaine; especially in poor neighborhoods; stiffer sentencing

What was used in many products by the late 1800s?

Coca/cocaine (think coca-cola)

What local effect does cocaine have (What DEA schedule)?

Anesthetic; schedule II

Primary Mechanism of cocaine ?

Blocks monoamine transporters (ie DAT)

What mechanism do high doses of cocaine cause ?

inhibits voltage gated Na+ channels (involved in action potentials)

What two Routes deliver cocaine extremely fast?

Smoking & IV

What is the peak subjective effect for crack cocaine?

1-2 minutes

What is cocaines half-life?

.5-1.5 hours

The inactive metabolite (Benzoylecgonine) is detectable in urine for how long?

Several days; weeks for heavy users

The active metabolite (Cocaethylene) is formed how & What is the half-life?

when cocaines ethanol are ingested simultaneously ; longer half-life than cocaine

What are Amphetamines?

chemical family of synthetic and natural psychostimulants

What is Ephedrine?

comes from Ephedera (mormon Tea) plant; trad Chinese med for asthma colds

What are the two active components of Ephedra Plant?

Ephedrine and pseudoephedrine (decongestants)

Where does cathinone come from & how is it taken ?

"khat" or "qat" scrub leaves & chewed

What are two synthetic variants of Cathinone ?

Methcathinone ("cat") and Mephadrone ("meow meow"); household products like bath salts; DEA schedule I

How were Amphetamines Methamphetamine used in the 1920's-30's , 1940's, & 1970's ?

1920's - > medical use developed, Benzedrine inhaler, narcolepsy; 1940's -> widespread during WWI; 1970's - Peak use of "speed

What are the synthetic forms of Amphetamines?

D - Amphetamine, L-Amphetamine, & Amphetamine (Adderall); Oral or injection (IV, SC)

forms of synthetic Methamphetamines ?

Methamphetamine (meth) ; most potent; oral, snorted, injected IV, or smoked