Term
| True/False: Cocaine is sufficiently lipophilic that it passes readily through the BBB |
|
Definition
| TRUE: Cocaine is sufficiently lipophilic that it passes readily through the BBB |
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Term
| Important factor in the strong addictive properties of crack cocaine |
|
Definition
| its rapid entry into the circulation (cocaine is lipophilic and smoking directs drug right to the brain) |
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Term
|
Definition
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|
Term
| Major metabolite of cocaine in heavy cocaine users |
|
Definition
| Benzoylecgonine (can be detected in urine for days after last dose) |
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Term
| Taking cocaine and alcohol together produce... |
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Definition
| Cocaethylene - biological activity is similar to cocaine and it has a longer half-life |
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Term
| Cocaine blocks the reuptake of |
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Definition
|
|
Term
| Does cocaine affect all monoamine transporters equally? |
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Definition
No - Cocaine binds most strongly to the 5-HT transporter, then the DA transporter, and then NE transporter
(but the blocking of DAT seems to be most important for cocaine's reinforcing properties) |
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Term
| How does cocaine act as a local anesthetic? |
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Definition
| At high concentrations, cocaine additionally inhibits voltage-gated Na+ channels in nerve cell axons (blocks nerve conduction) |
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Term
| Repetitive, seemingly aimless behaviors performed in a relatively invariant manner |
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Definition
| Focused sterotypies - seen in rats given increasing doses of cocaine |
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Term
| Subjects initially trained on cocaine readily generalize to...but much less generalization to... |
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Definition
| Subjects initially trained on cocaine readily generalize to amphetamines, but much much less generalization to caffeine (caffeine exerts its behavioral effects by a difference mechanism than cocaine or amphetamine) |
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Term
| Cocaine is a sympathomimetic drug which means... |
|
Definition
| that it produces symptoms of sympathetic nervous system activation |
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|
Term
| The physiological consequences of acute cocaine administration are...(4) |
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Definition
| increased heart rate, vasoconstriction, hypertension, and hyperthermia |
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Term
| Psychostimulant injection into the nucleus accumbens produces....while injection in into the striatum produces... |
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Definition
| Psychostimulant injection directly into the NAc elicits a locomotor response, while injection directly in the striatum elicits stereotyped behavior |
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Term
| True/False: Rats self-administer amphetamine into the NAc but not cocaine |
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Definition
| TRUE: Rats self-administer amphetamines directly into the NAc but do not self-administer cocaine directly into the NAc |
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|
Term
| One neurochemical difference b/w cocaine and amphetamines |
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Definition
| Amphetamines block DA reuptake as well as stimulate DA release...Cocaine only blocks DA reuptake (Also, amphetamines have no local anesthetic effects) |
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Term
| True/False: Cocaine reward is not present in DAT knockout mice |
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Definition
| FALSE...cocaine reward IS still present in DAT knockout mice (though they do not hyperactivity after treated with psychostimulants) |
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Term
| 6-OHDA lesions in the NAc causes... and 6-OHDA lesions in the striatum causes... |
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Definition
| 6-OHDA lesions in the NAc causes decreased locomotor response and decreased reinforcing effects following admin of psychostimulant. 6-OHDA lesions in the striatum causes decreased stereotyped behaviors following admin of psychostimulant |
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Term
| Do rats self-administer cocaine and amphetamine directly into the NAc? |
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Definition
| They self-admin amphetamine but NOT cocaine directly into the NAc...not really sure why |
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Term
| What were the results of SERT k/o mice experiments in regards to cocaine reward? |
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Definition
| Like DAT KO mice, inactivation of SERT did not eliminate cocaine's reinforcing effects, but DAT/SERT k/os did exhibit deletion of reinforcing effects |
|
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Term
| Fluoxetine effects on DAT k/o mice...what does this say about SERT blocking effects in general? |
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Definition
| Fluoxetine is a SERT blocker...rewarding effects exhibited in DAT k/o mice but not in wildtype. This suggests that the blocking of SERT produces both rewarding and aversive effects that counterbalance e/o and that DAT blockade is critical for cocaine reward. |
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Term
| Why does smoking and IV injection of psychostimulants produce a greater addiction potential than other routes? |
|
Definition
| Fast entry into the brain and fast DAT blockage produces the intense and rapid "high" |
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Term
| How does baseline DA release levels affect the effects of cocaine? |
|
Definition
| Low baseline DA levels= little effect with cocaine..High baseline DA levels= greater effect with cocaine (more DA in the synaptic cleft, so more of an impact when cocaine blocks DAT) |
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Term
| True/False: D1 receptors are necessary for locomotor-stimulating effects of cocaine, but D2 are not. |
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Definition
| TRUE: D1 required for cocaine effects...D2 not |
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|
Term
| Changes seen in rats given continuous cocaine infusions and rats given a once-daily cocaine injection |
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Definition
| Continuous cocaine infusions leads to tolerance. Once-daily cocaine injections leads to behavioral sensitization. |
|
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Term
| Sensitization divided into 2 phases: |
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Definition
| 1.Induction (process by which sensitization is established) and 2.Expression (process by which the sensitized response is manifested) |
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Term
| Expression of sensitization of cocaine/amphetamine is dependent at least partly on the enhanced reactivity of... |
|
Definition
| dopaminergic nerve terminals in the NAc. |
|
|
Term
| How would using a D3 agonist help solve cocaine abuse? |
|
Definition
| The agonist would compete with DA for dopamine receptor sites, blunting the euphoric effects of cocaine...and it has a lower efficacy that DA so they would also have less of an abuse potential. |
|
|
Term
| Amphetamine compounds are structurally very similar to |
|
Definition
|
|
Term
| 2 natural occurring compounds very similar to amphetamine |
|
Definition
| Cathinone (found in khat) and Ephedrine (from ephedra vulgaris) |
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Term
| Amphetamine and methamphetamine are metabolized by ____ at a ___ rate.. The metabolites as well as some unmetabolized drug are excreted via... |
|
Definition
| Amphetamine and methamphetamine are metabolized by the liver at a slow rate. Metabolites as well as some unmetabolized drug are excreted via the urine. |
|
|
Term
| The elimination half-life of amphetamine |
|
Definition
| 7 to more than 30 hours depending on the pH of the urine. |
|
|
Term
| Mechanisms of amphetamine and methamphetamine action |
|
Definition
| Amphetamine and meth are indirect agonists of the catecholaminergic system..Blocks catecholamine reuptake and releases catecholamines. Also at very high doses, they can inhibit catecholamine metabolism by MAO |
|
|
Term
| How does amphetamine cause neuron to release more DA? |
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Definition
| Amphetamine enters the cell through DAT and doesn't allow DA to be packaged well into vesicles. Also, causes DAT to function in the reverse direction, increasing synaptic DA |
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|
Term
| Admin of multiple doses of meth to animals causes long-lasting reductions in... |
|
Definition
| DA, tyrosine hydroxylase (TH), and DAT in the striatum |
|
|
Term
| Decreases in NT transporters sometimes reflect the loss of... |
|
Definition
| the corresponding nerve fibers (with amphetamine, decrease of DAT density observed...possibly due loss of dopaminergic neurons) |
|
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Term
| MDMA differs from AMPH and meth in that its primary mode of action is... |
|
Definition
| to enhance the release of 5-HT and inihibit 5-HT reuptake (also enhances release of DA but not as much as 5-HT) |
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|
Term
| True/False: MDMA use does not lead to serotonergic abnormalities. |
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Definition
| FALSE...MDMA use DOES lead to serotonergic abnormalities that may be indicative of actual damage to the nerve cells. |
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Term
| Cocaine is an alkaloid in the leaves of..and what percent is it of the leaves? |
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Definition
| Cocaine is an alkaloid in the leaves of the Erythoxylon Coca (~0.5-1.8%) |
|
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Term
| True/False: Cocaine is a weak base. |
|
Definition
| TRUE: Cocaine is a weak base so the coca leaves are chewed with lime or ash to increase the pH of the saliva to increase absorption in the stomach |
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|
Term
| Until 1903, Coca-Cola had how much cocaine per serving? |
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Definition
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Term
| To get initial extraction of cocaine, the leaves are mixed with...This produces a cocaine paste which contains how much cocaine sulphate? |
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Definition
| Leaves mixed with dilute sulphuric acid. The cocaine paste contains 20-80% cocaine sulphate |
|
|
Term
| How is the white powder form of cocaine formed? |
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Definition
| By washing the cocaine paste with kerosene which extracts cocaine HCl. |
|
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Term
| How much cocaine is enters the blood stream when cocaine salt (cocaine HCl, white powder form) is snorted? And why is smoking cocaine inefficient? |
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Definition
| 20-30% enters the bloodstream when snorting the cocaine salt. Smoking is inefficient because the vaporization temperature of cocaine is very close to the burning temperature. |
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Term
| How is cocaine free base made? |
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Definition
| Cocaine free base is made by adding water, base (e.g. ammonia) and ether. It has a lower melting point so it can be vaporized and inhaled. |
|
|
Term
|
Definition
| "Crack" cocaine is a cruder preparation of free base but made with baking soda and no solvent (not flammable) and it is only 75-90% pure. |
|
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Term
| How long does free base/crack take to reach the brain and how long does the peak take to set in and how long does the high last? |
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Definition
| Takes seconds to reach the brain. The peak effect is at ~1-2 minutes..whole high is over within 5-15 minutes. |
|
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Term
| True/False: Human users and lab animals do not discriminate between cocaine and other psychostimulants when given through IV. |
|
Definition
|
|
Term
| What monoamine transporters does cocaine block? and which is it most potent at? |
|
Definition
| DAT, NERT, and SERT; most potent at NERT |
|
|
Term
| True/False: Mice lacking DAT are spontaneously hyperactive (as if they were on cocaine) |
|
Definition
|
|
Term
|
Definition
| A synthetic variant of cathinone (methcathinone) ...very similar to other illicit stimulants. |
|
|
Term
| How is ephedrine and pseudoephedrine used as decongestants? |
|
Definition
| They constrict nasal blood vessels and decrease inflammation |
|
|
Term
| What is the base structure of amphetamines? |
|
Definition
| Phenethylamine (also is the structural backbone of DA) |
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Term
| Cocaine compared to AMPH/METH increases synaptic DA levels by how much? |
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Definition
| Cocaine produces a 2-3 fold increase in striatal DA release...AMPH/METH can cause >10 fold increase in extracellular DA |
|
|
Term
| How is locomotor activity effected at VERY high doses of AMPH? |
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Definition
| Locomotor activity actually goes down (because stereotyped behaviors increase) |
|
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Term
| D1 Receptors (D1,D5) are coupled to...and D2 Receptors (D2,D3,D4) are coupled to.. |
|
Definition
| D1 receptors coupled to stimulatory G proteins (stimulated AC) and D2 receptors coupled to inhibitory G proteins (inhibits AC) |
|
|
Term
| In primates, cortical DA receptors are concentrated in... |
|
Definition
|
|
Term
| This is the major target of DA in the brain...DA receptors are essentially concentrated here. |
|
Definition
| The striatum (DA is especially important for striatal function) |
|
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Term
| The striatum gets excitatory (glutamate) input from...and receives are more diffuse modulatory input from... |
|
Definition
| The striatum gets excitatory (glutamate) input from all over the cortex, and receives more diffuse modulatory input from midbrain DA cells |
|
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Term
| What are the 3 parts of the striatum and what kind of input do they all receive? |
|
Definition
1.Putamen receives mostly sensorimotor input.
2.Caudate receives cognitive input.
3.Accumbens receives emotional input. |
|
|
Term
| The striatum is part of...which plays a key role in... |
|
Definition
| The striatum is a part of the Basal Ganglia which plays a key role in CHOICEs. |
|
|
Term
| Simplified anatomy of the cortical-basal ganglia loops: |
|
Definition
| Thalamus->Cortex->Striatum->Pallidum->back to the thalamus |
|
|
Term
| In the striatum, how many neurons express D1 receptors and how many express D2 receptors? |
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Definition
| In the striatum, about half of the neurons express D1 and half express D2 |
|
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Term
| D1 and D2 cells of the striatum form distinct pathways to targets elsewhere in the basal ganglia..where are these? |
|
Definition
| D1 cells form pathways to the substantia nigra, while D2 receptors form pathways to the globus pallidus |
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Term
| What is the COMBINED effect of increasing striatal dopamine (in regards to D1/D2 activation)? |
|
Definition
| Enhancement of the "GO" pathway and inhibition of the "STOP" pathway (this is the opposite in Parkinson's Disease and with D2 antagonists like haloperidol) |
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Term
| In rats, drug-enhanced DA release in _____ is responsible for stereotypies. |
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Definition
| In rates, drug-enhanced DA release in the dorsal/lateral (putamen - sensorimotor) parts of the striatum is responsible for stereotypies. |
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|
Term
| Drug-enhanced DA release in _____ results in increased locomotion and motivation. |
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Definition
| Drug-induced DA release in the ventral/medial (NAc - cognitive/emotional) parts of the striatum results in increased locomotion and motivation. |
|
|
Term
| In response to PROLONGED elevations of DA, D1 striatal neurons... |
|
Definition
| increase their expression of dynorphin (dynorphin acts at DA terminals to reduce release..=crash) |
|
|
Term
| Influence of increased beta-endorphin levels after cocaine infusion on the "crash" |
|
Definition
| Increased beta-endorphin inhibits GABA (GABA usually inhibits DA neurons bu) so now DA neurons are excited...produce LOTS of DA which signals dynorphin to reduce release of DA..causing "crash" |
|
|
Term
| How long can amphetamine sensitization last in a rat? |
|
Definition
|
|
Term
| In humans, sensitization to amphetamines is seen in the form of increasing... |
|
Definition
| psychotic effects of the stimulants |
|
|
Term
| Endogenous opioid that works at kappa receptors and has aversive effects |
|
Definition
| Dynorphin (reduces DA signaling when DA is very high) |
|
|
Term
|
Definition
| Feeling of ants crawling all over you |
|
|
Term
|
Definition
| Event that alters the chance of an action being repeated (can be good or bad) |
|
|
Term
| what is Thorndike's Law of Effect? |
|
Definition
| An action that is followed by a satisfying event is more likely to be subsequently repeated. |
|
|
Term
| Where are effective self-stimulating sites particularly clustered? |
|
Definition
| Along the DA pathway from the midbrain (SNr, VTA) to the striatum. |
|
|
Term
| ICSS results suggest that this DA pathway might normally be used as a reinforcement signal. |
|
Definition
| The Nigrostriatal DA Pathway |
|
|
Term
| True/False: Midbrain DA neurons respond to unexpected natural rewards or reward-related stimuli. |
|
Definition
| TRUE: Midbrain DA neurons respond to unexpected natural rewards or reward-related stimuli..**Rewarding events that are fully predicted DON'T increase DA cell firing** |
|
|
Term
| DA cells "expect" rewards...so giving an unexpected reward to an animal has what effect on DA cell firing? how about giving an expected reward (after trained)? or omitting a reward that the animal was expecting? how about changing the time at which the reward is given? |
|
Definition
| Unexpected rewards-> bursts in DA cell firing. After being trained and receiving expected reward-> no change in DA cell firing. Omitting an expected reward-> pause in DA cell firing. Changing the time at which the reward is given-> burst in DA cell firing. |
|
|
Term
| On striatal neuron spines (on the dendrites), Glutamate inputs from cortex synapse where? and where do DA inputs often synapse? |
|
Definition
| Glutamate inputs from the cortex synapse on the spine heads...DA inputs often synapse on the necks of the spines. |
|
|
Term
| The LTP produced by DA D1 agonists is really caused by... |
|
Definition
| a change in connection strength of the glutamate synapse (not the DA synapses themselves) ..heterosynaptic plasticity..**The DA synapse is affecting the strength of the OTHER (glutamate) synaps** |
|
|
Term
| Brain stimulation that supports ICSS is also effective at enhancing the strength of... |
|
Definition
|
|
Term
| ICSS and striatal plasticity require... |
|
Definition
|
|
Term
| What does DA and Glutamate have to do with each other in regards to synaptic plasticity? |
|
Definition
| DA and glutamate signals act COOPERATIVELY to alter gene expression...some of these alterations act to consolidate synaptic changes. |
|
|
Term
| True/False: Abused drugs can induce transient expression of many genes in the striatum. |
|
Definition
| TRUE: Abused drugs can induce transient expression of many genes in the striatum..the set of induced genes includes many thought to regulate synaptic plasticity. |
|
|
Term
| True/False: Spine density of striatal and some cortical neurone increases after treatment with amphetamine or cocaine. |
|
Definition
| TRUE: The drug treated animals had increased spinal density in the striatum (and in parts of the cortex too) |
|
|
Term
| Why does spaced-out drug administration result in sensitization but frequent drug administration can lead to tolerance? |
|
Definition
| With frequent drug administration, the compensatory responses build up and can blunt the effects of the subsequent drug (tolerance)...when drug administration is spaced-out, the compensatory changes have time to dissipate before the next drug administration. |
|
|
Term
| Intense DA pulses produce long-lasting synaptic changes, that underlie... |
|
Definition
|
|
Term
| Two things that we have strong evidence of DA in the striatum doing. |
|
Definition
1.DA in the striatum is critical for psychomotor activation (movement,motivation,effort)
2.DA in the striatum is a critical learning signal (reward prediction error) |
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