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Cocaine binds with the highest affinity to...5-HT Transporter (SERT)Blocking __ ________ appears to be most important for cocaine's stimulating, reinforcing, and addictive propertiesDA reuptakeHow do we know it is inhibition of DA reuptake that mediates the psychoactive effects?- SSRIs and SNRIs do not produce psychostimulant effects
- DAT KO Mice display no further cocaine-induced increase in activity
- SERT KO and NET KO show cocaine-induced increases in activity
- destruction of NET nerve fibers has little effect on psychostimulant effects of cocaine
- destruction of DAT nerve fibers does not produce psychostimulant effects following cocaine administrationAt high concentrations, cocaine inhibits...voltage-gated Na+ channelsHow does cocaine act as a local anesthetic?prevents transmission of signals along sensory nervesWhich of the following statements about crack cocaine is FALSE?:
A) Crack cocaine is typically more expensive than powdered cocaine
B) Crack cocaine is produced by mixing dissolved powdered cocaine with baking soda, then heating and drying the cocaine/baking soda mixture
C) Crack cocaine resists heat much more effectively than powdered cocaine
D) Crack cocaine produces a profound and instantaneous euphoria, making it intensely rewarding and addicting
E) The US legal system penalizes users of crack cocaine more severely than users of powdered cocaineA) Crack cocaine is typically more expensive than powdered cocaineShort-term effects of cocaineextreme happiness, energy, mental alertness, hypersensitivity to sight, sound, and touch, irritability, paranoia, helps some people perform simple physical and mental tasks more quickly.Reinforcing effects of cocainerats will self-administer cocaine directly into NAccRe-instatement of cocaine-seeking behavior in previously extinguished animals>>>stimulated by microinjection of DA receptor agonists directly into the NAccMutant mice expressing a cocaine-insensitive DAT show ________ cocaine self-administrationreducedUnlimited access in primates and rodents leads to ________ self-administrationcontinuousCocaine has a ___________ than saccharinehigher breaking pointCocaine activates the sympathetic NS (sympathomimetic) which...increases heart rate, causes vasoconstriction, hypertension, and hyperthermiaIn rats, low cocaine responders (LCR)...have higher basal numbers of striatal DAT than the high cocaine responder rats.LCRs' basal numbers of striatal DAT ____ influence extracellular DA levels, DA signaling, or locomotor behavior ___________did not/ under drug-free conditionsAcute cocaine challengeLower number of re-uptake sites in HCR group resulted in more synaptic DA in HCR groupIn humans, intensity of the "high" depends on amount of ___________ and _________ and _________DAT occupancy (needs to be ~50%); Rate at which DAT occupancy occurs; Baseline level of DA release in the mesolimbic pathwayLow baseline DA releaseHigh baseline DA releaseIndividual differences in baseline levels of DA release may...Account for susceptibility to abuseYou are performing a genomic analysis of genes in the DA system. In one cohort of 200 humans that are not drug users, you find that 100 have a polymorphism in the DAT gene that results in significantly increased levels of DAT (compared with the other 100 subjects). The (High DAT Group/ Low DAT group) will have a greater behavioral response to cocaine challenge. This is due to the finding that a(n) (increased/reduced) # of reuptake sites in low DAT group results in more synaptic DA following cocaine challenge.Low DAT Group; ReducedCapture ratio of cocaine~15% of initial intranasal users become abusers"Incubation" of cocaine cravingcraving and relapse increase over time following withdrawalAbnormal function of ______ in patients with cocaine dependencyPrefrontal CortexAdaptations in the NAcc underlying tolerance due to long-access cocaine self-administrationModeling the transition from recreational to compulsive usePET imaging of cocaine-dependent individualsBaseline D2 receptor binding is ________ in the cocaine-dependent subjectsReducedMP (Methylphenidate) has a _______ in the control subjectsGreater effectDA system in cocaine-dependent individuals is _______________ to DA reuptake blockingLess responsiveRaclopride...Binds to D2 receptors and is displaced by released DATwo group of rats are being tested: 1) Group A is given extended access (6hr/day) to self-administer cocaine over 12 sessions; 2) Group B is given brief access (1hr/day) to self-administer cocaine over 12 sessions. Group A will show a(n) (increase/decrease/no change) in the threshold for ICSS over the course of the 12 sessions; Group B will show a(n) (increase/decrease/no change) in the threshold for ICSS over the course of the 12 sessions.increase; no changeGLP-1Neuropeptide; produced in the nucleus tractus solitarius (NTS) of hindbrainGLP-1 neurons in NTS send...Direct projections to VTA and nucleus accumbensAdministration of a GLP-1 receptor agonist (Exendin-4) directly into the VTAReduces intake of palatable foodAdministration of GLP-1 Agonist Exendin-4 (Byetta) into VTA and NAcc...Attenuates cocaine seeking behaviors during relapseIntra-VTA administration of a GLP-1 antagonist....Blocks the effects of Exendin-4 on cocaine seeking behaviors during relapseCocaine vaccine?Produces anti-cocaine antibodies & prevents drug from crossing blood-brain barrierPrevious work has shown that GLP-1 agonist drugs (reduce/increase) the intake of palatable food. In the brain, GLP-1 is produced by neurons in the (NTS/Amygdala/hippocampus) which sends projections to structures in the (mesolimbic DA circuit/mesocortical DA circuit/nigrostriatal DA circuit).reduce; NTS; mesolimbic DA circuitAmphetamineSynthetic derivative of phenylethylamine; parent compound of a family of synthetic psychostimulants that are structurally related to DANatural amphetaminesCathinone, ephedrine, pseudoephedrineMethamphetamine hydrochloride (HCL) in a _________Crystalline formAmphetamine and methamphetamine are metabolized by the liver at _____________A slow rateHalf-lives?Amphetamine: 6 hours
Methamphetamine: 12 hoursAmphetamine and methamphetamine are indirect...Agonists of the Catecholaminergic systemstwo modes of action...1.enter DA (NE) nerve terminals via uptake by DAT (NET) and cause vesicles to release DA (NE) into cytoplasm
2. Reversal of DAT (NET)Therapeutic uses of amphetamines...Nasal and bronchial decongestants, narcolepsy, appetite suppression and weight lossPsychostimulants (methylphenidate) in low doses produce a __________ in more than half of children with ADHDCalming effectStimulant Meds for ADHDDexedrine, Adderall, Vynase (amphetamines)Non-stimulant Meds for ADHDStrattera: NET inhibitor, Intuniv: a2 agonistHypothesis: DA and NE activity in the PFC is....Deficient in patients with ADHDPFC functioning is an _________ function mediated by the activity of catecholaminergic systemsinverted U-shapedADHD meds enhance _______________ in the PFC to restore balanceCatecholaminergic activityThe pyramidal neurons of the PFC are innervated byNoradrenergic and dopaminergic axonsNE activation of α2A receptors ________ the strength of _____ sensory input (increases signal)enhances; relevantDA activation of D1 receptors ___________ sensory input (decreases noise)weakens irrelevantMethylphetamate increases extracellular...NE and DA levels•α2A inhibits cAMP production in spines, where cAMP signaling can open potassium that weaken network connectivity
•stimulation of D1 receptors increases cAMP signaling in spines, weakening inappropriate responsesAmphetamine-induced psychosisProvided initial impetus and support for the DA hypothesis of SchizophreniaMethamphetamine use causes damage to...DA axons and terminals; serotonergic fibers in several brain areasMethamphetamine-induced loss of tyrosine hydroxylase immunoreactivity in the nigrostriatal compared with the mesolimbic DA pathways in miceBrain imaging: reduction in striatal DAT binding with chronic methamphetamine and methcathinone use
Damage is similar in a Parkinson's disease patient, where the DA innervation of the striatum is known to be severely compromisedMeth mouth?The decaying of teeth due to decreased saliva production in meth usersSynthetic cathinonesChemically similar to amphetamines, cocaine, and MDMAYou are a physician examining a patient and notice that she has very bad teeth. The patient tells you that she is a methamphetamine addict. You explain to her that methamphetamine is a (parasympathomimetic/sympathomimetic/sympatholytic) drug that causes a(n) (increase/decrease/no change) in synaptic (NE/ACh/DA) levels in peripheral nerve terminals. This leads to a(n) (increase/decrease/no change) in secretions from salivary glands and contributes to poor oral hygiene.sympathomimetic; increase; DA; decreasePsychostimulant withdrawal often has ___ visible physical symptomsnoGawin and Kleber's Phasal Model of Cocaine Withdrawal (1986)
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Review of Cell Biology/Neurobiology
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