psychopharm test 2

how might some withdrawal symptoms of caffeine, like lethargy, be linked to tolerance?

If caffeine is blocking adenosine A2A receptors then the adenosine can inhibit dopamine from having any effect on the nearby dopamine receptor. This means the body will bind dopamine successfully more often, and thus there will likely be downregulation of dopamine receptors. So when caffeine use is stopped, one withdrawal symptom could be lethargy, as there is a lack of dopamine to help the reward system work and keep you motivated to do things. need to fact check this one with proffesor

how does taking a dopamine agonist affect the mesolimbic and nigrostriatal pathways, especially for those with parkinsons?

If the reason for parkinsons is that dopamine producing cells in the nigrostriatal pathway are dying, then giving someone a d2 agonist will help treat the effects of their disease. Reduces parkinsonian symptoms (nigrostriatal) Can induce positive symptoms (mesolimbic) Positive in this case means the presence of something that nobody else is experiencing. Can induce compulsive behavior When giving someone a drug that increases dopamine in one pathway, you cant control which pathway the dopamine goes into. So those taking d2 agonists will have extra dopamine going into the mesolimbic pathway as well, causing hallucinations.

where does tolerance come from in caffeine?

In experimental tests: there is evidence of adenosine receptor upregulation in rats as a result of chronic exposure to caffeine. There was also evidence of a decreased affinity between caffeine and A2A receptors, meaning it gets less good at binding to those receptors. Why upregulation? Because caffeine is working by blocking adenosine receptors. The cell sees that "i should be inhibited by adenosine, and im not getting it." So it decides it needs to do shit that increases the odds of adenosine binding to the cell. So it creates more adenosine receptors to increase odds that the A will bind to it.

what is incentive salience and incentive sensitization and how does that relate to dopamine and to the motivational component of reward?

Incentive salience: The psychological process leading to drug "wanting" (i.e. craving). It is called incentive salience because it is a process whereby certain stimuli (in this case external and internal stimuli associated with drug use) become extremely salient (attention getting) and acquire incentive (are attractive and desirable) properties. key component of the incentive sensitization theory of addiction which hinges on there being a difference between drug liking (the high) and drug wanting (craving). The theory says that there is a marked increasing in "wanting" with repeated drug use even if there is no change or even decrease in the "liking" This is thought to happen because drug "wanting" and the drug "liking" come from different systems. The drug causes a sensitization in the wanting system and no change or tolerance in "liking" system. Liking system = the hedonic hot spots, where local stimulation produces pleasurable effect. Wanting system is a more widespread circuit that includes the mesolimbic DA pathway

what are the ways caffeine affects behavioral and cognitive performance at a healthy dose?

Increased arousal Increased cognitive ability Increased mood Increased atheltic performance Decreased pain

Cocaine is taken intravenous, smoked, intranasal, and oral. compare and contrast these routes of administration in terms of addiction potential, intensity of high, duration and which is the most popular.

Intranasal is the most popular, lasts longest and has a higher faster spike then smoked and oral. Smoked is crack/freebasing: it lasts longer then IV, less intense feeling but fairly fast. IV is super fast and the pleasure peak is HUGE, but it decays really fast. Oral's main weakness is the onset is super slow. injection and smoking are more addictive because It is generally agreed that the more quickly a drug is delivered to the brain, the more likely it will lead to dependence..

what is the learning component of reward and what evidence is there regarding the role of dopamine in the learning component of reward?

Learning component of reward: Reward expectancy:the expectation that a particular action will lead to attainment of an incentive Reward learning: strengthening of specific-stimulus response associations based on delivery of the incentive. Does dopamine help us learn what stimuli or actions lead to reward? You get an increased firing rate of dopamine neurons after the presentation of a novel stimulus. Dopamine really likes dopamine. The increased firing rate also happens after doing things that lead to the euphoric effect (not the effect itself, just things that lead to it) You can have an increased firing rate after a conditioned stimulus which signals the euphoric effect. If you are hit with a conditioned stimulus that normally signals a euphoric effect: your fire rate will increase. But if there is no actual reward then there will be a decrease in firing rate. So dopamine is trying to predict euphoric activities, and motivate the system to go and do them. Its helping us become reward detectors, and that is EXTREMELY EVOLUTIONARILY BENEFICIAL. In a sense: addiction is a pathological form of learning

what is the location of the anti-reward system?

Located in the extended amygdala, which includes the bed nucleus of the amygdala, and a part of the nucleus accumbens.

what do lesions of and microinjections of cocaine into the nucleus accumbens and striatum do?

Microinjection of cocaine in NAcc -> increased locomotor behavior (drug seeking) Lesion to NAcc -> decreased locomotor behavior even when given stimulant. These two observations suggest that the NAcc is very important for drug seeking behavior. Microinjection of cocaine in NAcc -> reinforces operant behavior Lesion to NAcc -> decreased reinforcement from cocaine. Microinjection of cocaine into striatum -> increased stereotyped behaviors Lesion to striatum -> decreased stereotyped behaviors, even when given stimulant Positive relationship between dopamine in striatum and craving for drug when presented with cues related to cocaine.

Ultimate bioavailability of caffeine and why that is

No first pass metabolism. It does pass through liver it just DOESN'T DO ANYTHING We don't actually know what happens in first pass metabolism we measure whether it happens or not based on our measured bioavailability in the body. Almost completely bioavailable (99%) similar to IV

what pharmacokinetic factors might happen to adenosine receptors to influence tolerance during repeated caffeine use?

Pharmacodynamic tolerance: tolerance as a result of upregulation or downregulation of neurotransmitters. For caffeine it is upregulation since caffeine blocks adenosine receptors and in response to their being not enough adenosine activating receptors the body will upregulate. For a drug like nicotine it would be down regulation because there is too much activation of receptors.

what are the hedonic hotspots and what role do they play in reward

Pleasure hot spots: A system of small hedonic hot spots, unrelated to dopamine, provide temporary sensations of pleasure and forms a feedback loop with the reward system that controls desire. This is a part of the opioid system. Brain stem: basic visceral sensations and reactions to pleasure, instincts like smiling originate at this spot. Ventral pallidum: animal experiments show that damaging this hot spot can turn something that once gave pleasure into a source of disgust. Essentially, we don't know why yet, but an intact one is integral for normal reward and motivation. Nucleus accumbens(NAcc): a hot spot within this key part of the craving circuitry amplifies the response to pleasure. Orbitofrontal cortex: this hot spot gives a sense of gratification but is also the first to shut down if a person indulges too much.

How does the biopsychosocial model help to explain addiction?

Positive reinforcing effects of drugs increase frequency of drug taking behavior by rewarding it. Negative reinforcing effects of drug take away good feelings when use stops, thus increasing frequency of drug taking behavior. Drug use will turn the context of drug use into a discriminative stimulus that increases frequency of drug taking behavior just by being near it. Risk factors like a different number of receptors, genetic variations, or being socialized to believe certain drug use is more acceptable increase likelihood of addiction Adverse effects of drugs decrease chance of addiction Protective factors can reduce the likelihood of an individual becoming addicted or can help prevent relapse in drug users attempting to maintain sobriety. Things like your personality, social/family life, and day to day environment. Things like rehab can help beating an addiction stick because of the controlled environment.

Nigrostriatal pathway: where does it originate and where does it terminate?

Projects from substantia nigra Projects to striatum (composed of two smaller nuclei we call the caudate nucleus + putamen) Striatum is part of the basal ganglia Caudate nucleus and striatum are used interchangeably when talking about pathways.

Mesolimbic pathway: where does it originate and where does it terminate?

Projects from ventral tegmental area (VTA) (it's in the midbrain) Projects to limbic system (especially nucleus accumbens: NA)

what is dopamine's role in reward learning?

Reward learning: Under baseline conditions, midbrain dopamine cells in monkeys fire intermittently at a low fire rate. Brief bursts of dopamine neural firing occur in response to novel stimuli or an unexpected reward. If the reward is paired with a conditioned stimulus using classical conditioning so that CS predicts reward, then the CS will cause the dopamine neural firing before the reward is even giving. If the reward is paired with a conditioned stimulus using classical conditioning so that CS predicts reward, and then you present the CS but DO NOT GIVE THE REWARD. Then there will be a dip in cell firing rate. So the point of the DA neuronal firing is to signal the difference between prediction and actual occurrence of rewards. In other words the DA firing exists so that the brain can remember if the reward was predicted correctly or wrongly(reward-prediction error).

what is an SNP and what does the common SNP in the human D2 receptor do?

SNP: single nucleotide polymorphisms, where a single nucleotide changes the who sequence of an amino acid and thereby changes how it functions. A SNP in the gene for human D2 receptors causes a reduction inDA binding. Carriers of this form of the receptor appear to exhibit poorer cognitive function and may be at increased risk for ADHD. (gluskin and Mickey 2016)

Be able to provide evidence that dopamine in the striatum is linked to drug craving and be able to describe the study that shows that

Studies show that DA release is increased in the dorsal and ventral striatum when cocaine users are presented with cocaine related stimuli such as video tapes of people smoking cocaine or crack pipes. The study that found this did PET imaging scans of the persons brain while they were watching the cocaine cues. They gave them radiolabeled raclopride, which is a chemical that binds to D2 receptors and then gets displaced when dopamine binds to the receptors. So they can track dopamine binding by measuring how many and how often the radiolabeled racloprides get displaced. The subjects were asked to rate how much they were craving cocaine as the video went on. There subjective ratings are compared with the amount of dopamine binding and it shows there is a positive relationship between the amount of dopamine binding in the striatum and the craving ratings.

what does it mean that cocaine is sympathomimetic?

Sympathomimetic-produces symptoms of sympathetic nervous system activation Increased heart rate and blood pressure High dose can be fatal (seizure, heart failure) sympathetic nervous system, directs the body's rapid involuntary response to dangerous or stressful situations. Cocaine blocks the reuptake of norepinephrine, increasing the amount of norepinephrine in cleft. (this is why it affects the sympathetic nervous system)

what are the two dopamine receptor families? which dopamine receptors are in each family? how do their functions differ when activated?

The D1 like receptor family act very similar to each other. D1 D5 The D2 like receptor family D2 D3 D4 They are called D1, and D2 like because those 2 were discovered first. Dopamine activating D1 receptors activates the Gs g protein which increases synthezation rate of cAMP Dopamine activating D2 receptors activates the Gi g protein which decreases synthezation rate of cAMP In some cells, D2 receptor simulation activates a G protein that subsequently enhances K+ channel opening, which causes hyperpolarization and decreases the excitability and firing rate of the cell.

what do we mean by the dopamine reward pathway and how is it linked to the mesolimbic pathway?

The dopamine reward pathway, is the parts of the reward pathway that work because of dopamine such as the mesolimbic and mesocortical da pathways. Essentially the mesolimbic pathway is the dopamine reward pathway. The mesolimbic pathway from the VTA to the NAcc has a central role in drug reward and reinforcement. Nearly all drugs of abuse activate this pathway either by enhancing VTA cell firing or by increasing the amount of dopamine floating around outside of cells in the NAcc.

what is the role of CYP1A2 in the metabolism of caffeine and factors that can influence that enzyme and thus metabolism?

The enzyme primarily responsible for breaking down caffeine is CYP1A2. Caffeine does not lead to CYP1A2 enzyme induction, BUT Tobacco smoke does lead to CYP1A2 enzyme induction. Oral contraceptives/pregnancy can inhibit CYP1A2 Multiple genetic variations 95% excreted via urine.

what is the motivational component of reward and what evidence is there regarding the role of dopamine in the motivational component of reward?

The motivational component of reward Drug wanting: the desire to obtain various types of incentives (food, water, shelter, sexual partner, or drugs). Dopamine is the chemical that causes drug wanting. incentive salience: the ability of sensory stimuli to acquire strong motivational properties. For someone without an addiction if you see an ashtray you might not even notice it. For someone with an addiction the ashtray or other drug paraphernalia are much more attention grabbing. Incentive sensitization: over time, the "wanting" of a drug can increase while the "liking" can stay the same or even decrease. Drug seeking behavior:the goal directed actions aimed at obtaining incentives.

What are the 5 dopamine receptors?

The neurotransmitter dopamine (DA) uses 5 main subtypes, designated D1 to D5 They are all metabotropic receptors They interact with g proteins and they function, in part, through second messengers.

what is the opponent-process model of motivation and how does it relate to the reward and antireward systems?

The opponent process model: hypothesizes that the neural mechanisms responsible for afect (mood and emotion) were organized such that any stimulus that provokes an initial strong affective reaction (strong feelings of pleasure or discomfort) automatically sets in motion an opposing affective response that is experienced after the initial stimulus ends (like the recruitment of the antireward system). Later scientists applied this model to addiction. They hypothesize that a phenomenon called allostasis gradually changes the baseline hedonic state of the drug user. Allostasis is a biological concept in which a variable (physical/behavioral or psychological) that is repeatedly challenged maintains stability by changing its normal baseline in the absence of challenge. For addiction the allostasis would be the hedonic state variable is repeatedly challenged by drug exposure, and maintains its stability by changing its normal hedonic baseline level.

what do we know about how the route of administration for the drug affects chances of addiction?

The route of administration is not a property of the drug, it is a property of use of the drug Nicotine patches(transdermal) are less addictive than cigarettes (inhalation). the higher the bioavailability and the quicker the onset the higher the chance of addiction.

what evidence is there for withdrawal effects of caffeine?

There is evidence of withdrawal symptoms from caffeine. When subjects are unknowingly switched to placebo, adverse withdrawl effects spike, and then slowly go away over time. It makes sense that with caffeine, if you have upregulated all those adenosine receptors to compensate for all that caffeine in your system: suddenly not using caffeine will make it so that adenosine is binding like crazy and you will feel tired all the time.

mesolimbic pathway: what functions is it associated with and how is it linked to schizophrenia?

This is the reward and motivation pathway. Overactivity linked to positive symptoms of schizophrenia (hallucinations and delusions) Positive in this case means the presence of something that nobody else is experiencing.

what are the behavioral effects of cocaine?

Time distortion: rats who are trained to press a lever after 12 seconds, on cocaine will press it after 8 seconds. So it speeds up perception of time Increased heart rate and blood pressure Increased motor excitement, restlessness, compulsiveness. Insomnia, trouble sleeping Aggressiveness increase Overly talkative to rambling Inflated self esteem-delusions of grandeur Mood amplification: both good and bad.

what patterns of use lead to tolerance to cocaine's effects versus sensitization to cocaines effects?

Tolerance: reduced effect Tends to happen with continuous, long term use The locomotor effects and euphoria are the symptoms of the drug that start to go down with tolerance the most. Sensitization: increased effect Tends to happen with intermittent use Especially prominent with stereotyped behaviors and locomotor activity. Tolerance isn't always what happens, its all about the pattern of use when it comes to locomotor activity, however this sensitization doesn't really happen with the euphoria symptom.

what is the effect of adenosine at A1 receptors?

When adenosine binds to an A1 receptor, it prevents Ca2+ influx. Ca2+ opens calcium channels which release neurotransmitters in a presynaptic nerve. So when adenosine binds it reduces the amount of neurotransmitters released.

what role do positive and negative reinforcement play in addiction?

Withdrawal acts as negative reinforcement because the bad experience (withdrawal) is being taken away when you take the drug: rewarding the behavior. Naive drug taking is positive reinforcement because a good experience (drug high) is being introduced when you take the drug: rewarding the behavior.

what are withdrawal symptoms from cocaine and how that might be linked to neuroadaptive changes in the dopaminergic system?

Withdrawal isn't really a big contributing factor with cocaine. physical dependence doesn't play into what makes addicts want to resume drug taking behavior as much with cocaine. Stage 1: crash (agitation, drowsiness, intense cocaine cravings) Stage 2: withdrawal: (lethargy, anxiety, recurrent cravings, high vulnerability to relapse) Stage 3: extinction (patient remains highly vulnerable to cravings and relapse triggers) Withdrawal is defined a lot by the tolerance effect of baseline being shifted down because of your now downregulate dopamine system.

Common disease-common variant hypothesis:

according to this hypothesis, the genetically based susceptibility to a particular neuropsychiatric disorder stems from a pool of risk-granting gene alleles that are possessed in common throughout the population. Each of these risk alleles that you may carry grant a small increase in susceptibility to developing a disorder, in this case substance abuse disorder. Your overall susceptibility is determined by the sum of all the risk alleles you carry.

how do we know that binding to adenosine receptors is the most likely candidate as a mechanism of action for caffeine?

because there have been studies showing that the amount of adenosine outside the cell is massively increased during periods of wakefulness following a caffeine dose, and also just when people report to be awake.

explain the graph on the other end

caffeine/caffeine 20 days of caffeine pills, 20 days of caffeine pills. placebo/caffeine: 20 days of placebo pills, 20 days of caffeine pills. Etc. When asked how peppy they feel: people in plac/caff give higher ratings then other combinations. Those who take caffine the whole time develop a tolerance effect and give the same rating as caff/plac group since the 10mg of caffeine or whatever doesn't really have an effect any more.

what are the primary mechanisms of action of cocaine on the monoamine systems, especially dopamine?

cocaine blocks the reuptake of 3 monoamines, serotonin, norepinephrine, and dopamine, by binding to their transporter proteins and inhibiting their function/ this results in an increase in the amount of these monoamines outside cells. the extra norepinephrine activates the sympathetic nervous system. the extra dopamine causes increased locomotion.

what does the rat park vs rat cage with nothing but a heroin drip in it tell use about how the drug users environment impacts addiction?

if they have no other option they are more likely to become dependent. rats in the rat park with a heroin drip are much MUCH less likely to become addicted then rats left alone with only the heroin drip to interact with. and rats left in cage with heroin drip that are super addicted can get over there addiction when placed into the rat park fairly quickly, even when there is a heroin drop available in the rat park.

reinforcer

in operant conditioning, any event that strengthens the behavior it follows. any drug where after doing it you are incentivised to use it further is acting as a reinforcer.

sterotyped behaviors

is a behavior that is repetitive, seemingly aimless behavior like mouthing objects, hand flapping, body rocking, repetitive finger movements, and or nonfunctional/non contextual repeated vocalizations

what is the location of the reward system?

located in the mesolimbic and mesocortical DA pathways that start in the ventral tegmental area of the midbrain and terminate in the nucleus accumbens, amygdala and frontal cortex. Other important connections: extended amygdala system which connects 3 things: the central nucleus of the amygdala , the shell of nucleus accumbens and the bed of the stria terminalis.

what is the most common route of administration for caffeine and why?

oral because caffeine has a very high bioavailability as it bypasses first pass metabolism since the liver just doesn't do anything.

how does cocaine effect time perception?

rats who are trained to press a lever after 12 seconds, on cocaine will press it after 8 seconds. So it speeds up perception of time

Common disease-rare variant hypothesis:

research shows that different individuals diagnosed with the same disorder may carry vastly different genetic profiles. So according to this hypothesis, a significant portion of the genetic risk for a neuropsychiatric disorder stems from rare mutations or other genetic anomalies. Alot of this research was not done on substance abuse disorder patients, but it is applicable.

what are the ways caffeine affects behavioral and cognitive performance at a toxic dose?

restlessness Nervousness Insomnia Increased heart rate Gastrointestinal problems Can be worse in people who already have anxiety

give an example of how a drug might act as a negative reinforcer and when that might explain escalating or continued drug use?

the removal of withdrawal symptoms is negative reinforcement, because it is removing a bad experience when you do the drug. which is what leads to a majority of continued use.

what is the difference between the reward and anti-reward system in terms of function?

the reward system functions as a way to reward desirable actions, and to motivate people to seek out desirable things. Activation of the antireward system leads to increased release of norepinephrine(NE) and two neuropeptides: corticotropin-releasing factor (CRF) and dynorphin. This system has two major functions: It puts a limit/brake on reward Mediates some of the adverse effects of stress such as increased anxiety. In a drug dependent person, the antireward system is activated during drug withdrawal and plays a major role in its adverse effects and the negative reinforcement when drug taking is resumed.

how are the reward system and anti-reward system recruited with naïve/non-dependent use?

the reward system is recruited when the drug is first taken creating a strong hedonic pleasurable response to give that drug high which shoots up pleasurable feelings. then in order to pump the brakes on that reward, the antireward system is recruited to bring that drug user back to hedonic baseline with a relatively weak opponent process.

what are the 3 changes on a pharmacokinetic level that lead to tolerance of cocaine

· Over time cocaine gets less effective at blocking reuptake, thus over time there is better clearance of dopamine over time. · Reduced dopamine synthesis and release over time with tolerance, since the cell realizes that there is already "plenty in cleft" so they don't need to produce as much. · There is also downregulation of dopamine receptors (D2) over time, since there is a lot of this neurotransmitter and the cell thinks it doesn't need that many receptors.

what are the indicators that we discussed in class (supported by the text) that help to determine whether someone is "addicted" to a substance.?

Abstinence from drug leading to withdrawal symptoms can be a sign of addiction: however physical dependence is not required for something to be considered addictive. Example: cocaine has no physical dependence, yet it's highly addictive. Features of addiction: (0) Maladaptive: interferes with and worsens ability to function in day to day life, social or what have you. (0) Relationship issues, (0) Failed obligations (0) Stopping activities (0) Cravings and compulsive drug seeking (0) Not talking to anyone, or being late for work just to get your drug fix. Just because you develop a tolerance doesn't mean you have an addiction. If you are addicted to something there is a high chance you will have a tolerance, but a tolerance in and of itself isnt an indicator if addiction.

give an example of how a drug might act as a positive reinforcer and when that might explain escalating or continued drug use?

Addictive drugs start by being positively reinforcing: they introduce a good experience after doing the drug, thus increasing frequency of use.

why does adenosine accumulate in our system during the day, and why it would be related to a pressure to feel sleepy?

Adenosine builds up in the brain during wakefulness as our body breaks down ATP for actions that require adenosine, then as we sleep it is cleared from the system. We have high levels of adenosine after being awake for a long time and low levels just after sleeping This is because your body as a whole is doing less energy-requiring cellular processes during sleep, and a lot more of them during the day. so the body can tell it need to rest and gather more energy because the byproduct of all their energy spending activities is reaching a really high level. like knowing you've eaten too many candies because your desk is covered in wrappers.

what is adenosine?

Adenosine is a neurotransmitter that is not synthesised by neurons, it is instead linked to ATP. ATP stands for Adenosine TriPhosphate. It is involved in almost every energy requiring action in the cells. It's called triphosphate because there are 3 phosphates bonded together. Essentially if you need to trigger a biological process that fights against the natural flow of particles, then you need to put in some energy. That energy comes from the breaking of the high energy phosphate bonds of ATP. After the phosphate groups are used for energy, you are left with adenosine as a byproduct. That is how the body gets its adenosine.

how are the reward system and anti-reward system recruited with dependent/repeated use?

As a naive user becomes a drug dependent user The hedonic baseline (O') has shifted downward so the recruitment of the reward system is much weaker and shorter and only really gets the user up to the old version of normal. The antireward system in an addict results in a strong and prolonged opponent response during withdrawal

what are the 3 factors that influence whether someone will report feeling "high" when taking a drug?

At least 40-60% Dopamine transporter protein occupancy needed for "high." if you have a lot of DAT's then it will be harder to get high since it will take more of the drug tor reach that 40-60% threshold. Rate at which the Dopamine transporter proteins are occupied (route of administration) Baseline level of dopamine. If someone already has high levels of dopamine then the effect of cocaine will be even greater.

Average half-life of caffeine and implications of that

Average half life is 4 hours. The implications of this are that it takes a fairly long time to clear caffeine from your system completely.

Site of absorption and approximate absorption time for caffeine

Begins in stomach but most of the caffeine is gonna be absorbed from the small intestine. Peak plasma concentration takes 15-20 minutes to achieve.

how does classical conditioning to caffeine's effects explain headaches during caffeine withdrawal? you should be able to readily identify the US/UR and CS/CR

Caffeine can also be classical conditioned. If you take caffeine, your blood vessels constrict, your body will dilate them to try to respond. If you drink coffee every morning in the same way, just doing your morning routine (even if you stop drinking caffeine) will cause your body to dilate the blood vessels. Dilating blood vessels when your muscles aren't actually constricting causes headaches. This is why caffeine headaches happen when people try to quit.

what is the main mechanism of action for how caffeine interacts with adenosine receptors and why does that result in the behavioral and physiological effects of caffeine?

Caffeine is a competitive antagonist, because its binding to adenosine receptors and triggering no response. Because adenosine is inhibitory and makes people more sleepy when it binds: preventing it from binding makes people more alert.

how can the environment and context associated with a drug affect addiction

Context associated with the drug can serve as a discriminative stimulus that indicates when reinforcement is likely to occur, making behavior more probable. A discriminative stimulus is a stimulus that tells you when a behavior will be reinforced. A red light is a discriminative stimulus for pushing your gas pedal. The owners being home is a discriminative stimulus for a dog getting on the furniture. When trying to abstain from a drug, it is better to not be in the same context as when you do the drug,

how does takinga dopamine antagonist affect the mesolimbic pathway and nigrostriatal pathways especially in those with schizophrenia?

D2 antagonist: Reduces positive symptoms of schizophrenia (less dopamine in mesolimbic pathway) Induces parkinsonian symptoms (less dopamine in nigrostriatal pathway, just like for those with parkinson's) Essentially, when treating a problem in one pathway, you inadvertently cause a problem in the other pathway. It's almost like taking a drug to trade mental disorders, only its reversible if you stop taking the drug.

Nigrostriatal pathway: what functions is it associated with and how is it linked to parkinson's disease?

Deals with initiating movement Learning that involves action and feedback This function is why this pathway is important in addiction Parkinson's disease: degeneration in nigrostriatal pathway This is why those with advanced parkinson's shuffle around with stuttered movement that is really slow to initiate. The basal ganglia is linked specifically to initiating movement

which reward pathways are the nucleus accumbens and the striatum in?

Down the mesolimbic pathway, there is a section of the brain called the nucleus accumbens (NAcc) Striatum is down the nigrostriatal pathway

what is the emotional component of reward means and what evidence is there regarding the role of dopamine in the emotional component of reward?

Emotional affective component of reward: subjective feelings of pleasure. Is dopamine the thing that makes us feel "Good" when we do a rewarding action? There is research that shows: no. Cocaine users that also take a dopamine suppressant at the same time (which prevents synthesis of dopamine) still report that taking cocaine makes them feel good compared with a control group. However: what the cocaine users said does change, is that they didn't feel motivated to take the drug again.Dopamine is not the emotional affective component.

Why is intranasal the most popular route of administration for cocaine?

Fairly quick onset of effects Duration of high is fairly long Is pretty high bioavail, not insane but fairly high. For cocaine entering into the nasal area, it's a powder so it mostly enters the bloodstream going through walls of nasal passages, and then because it's lipid soluble it goes through the blood brain barrier.

5 drugs that rate consistently as most addictive:

Heroin (opioids) Alcohol Cocaine Barbiturates nicotine

When you set a rat down in a new environment they will want to check out everything and they walk around everywhere. So when a rat is set in a cage their locomotion is very high at first, and then it will gradually decrease. Once rats have settled down: the experimenters give them either a cocaine or saline injection. Some rats got cocaine and reacted similarly to the control group, and some were super hyperactive. why?

How rats react to cocaine injections was based on the number of dopamine transporters the rats had. Rats who didn't react much to cocaine had more dopamine transporters then the rats who got super locomotive after getting cocaine. However: the rats with high transporter proteins dont act differently than rats with less transporter proteins at a baseline chemical balance. If you have more dopamine transporter proteins you are gonna be a low locomotion post cocaine because you are clearing the dopamine quicker.

what is the effect of adenosine at A2 receptors?

If adenosine binds to a A2AR receptor next to a dopamine receptor, it causes an allosteric effect on the nearby dopamine receptor, preventing dopamine binding to the dopamine receptor from having any effect.