18: Psychoactive Drugs

opiates (morphine, heroin)

-act on opiate receptors in the brain -yes, there are endogenous opiates in the brain, known as endorphins! -causes physical dependence and strong withdrawal symptoms

mechanism of action of nicotine

-attaches to one type of acetylcholine receptor called the nicotinic receptor, mimicking ACh action at these synapses (this occurs in both the CNS and peripheral NS)(the nicotine from one cigarette can occupy over 80% of the brain's nicotine receptors) -nicotine acts on nicotinic receptors in the ventral tegmental region to exert both its rewarding properties and its addictive properties. because nicotine stimulates the VTA, it causes the release of dopamine in the nucleus accumbens and therefore causes "wanting"

mechanism of action of cocaine & amphetamine

-cocaine blocks the reuptake transporters for catecholamines, including dopamine and norepinephrine -this slows reuptake, and makes dopamine act longer in the synapse -amphetamine also interferes with dopamine transporters but does so indirectly, by acting via intracellular molecular pathways to cause dopamine reuptake channels to be removed from the presynaptic membrane -actions of this type on dopamine activity in the nucleus accumbens (part of the reward pathway) are thought to be an integral part of cocaine & amphetamine's addictive effects -long term chronic use causes down regulation of postsynaptic dopamine receptors and tolerance to some effects of cocaine result

alcohol

-depressant -however, has a biphasic effect (initial stimulant effect, followed by depressant effects)

cocaine

-derived from the coca plant -known for its addictive properties (causes physical dependence and strong withdrawal symptoms) -used as a psychostimulant until amphetamine was synthesized (amphetamine was sold in inhalers for nasal congestion and its mechanism of action is similar to cocaine) -crack is a smokable form of cocaine (enters the blood and brain more rapidly in this form --> even more addictive)

what changes at the synapse lead to sensitization and tolerance?

-drugs may alter the number of postsynaptic receptors being expressed -synapses can down-regulate receptors in response to an agonist drug. too much stimulation causes the synapse to try to compensate and fewer receptors means less stimulation. if this happens, you need more drug to get similar stimulation (tolerance) -in response to a drug that is an antagonist, receptors up-regulate. this is too little stimulation causes receptors to seek stimulation and with more receptors expressed, less drug is needed (sensitization) ***remember: an antagonist can inhibit and inhibition therefore causes stimulation of neurons

mechanism of action of opiates

-endorphin synapses inhibit GABA transmission (which is an inhibitory neurotransmitter) in dopamine pathways -reducing inhibitory GABA transmission --> increased dopamine release

nicotine

-first encountered by explorers to the Americas because tobacco is a native american plant -strong stimulant (increases heart rate and blood pressure)

withdrawal symptoms

-occur if you are dependent on the drug -the unpleasant physical reaction that accompanies the process of ceasing to take an addictive drug

sensitization

-occurs when the drug effects become stronger with repeated treatment

mechanism of action of amphetamine & methamphetamine

-particularly potent -not only increase the amount of neurotransmitters that are released when a neuron fires, but they can also stimulate neurotransmitter release in the absence of an action potential -also known to (like cocaine) block reuptake of neurotransmitters and can interfere with degradation of neurotransmitters in the synaptic cleft -with these effects combined, there is a lot more dopamine in the synapse and a lot more stimulation of dopamine receptors

tolerance

-successive treatments have decreasing effects, so more drug is needed to get the same rewarding properties -ex. drugs like cocaine cause a loss of receptors for dopamine because of negative feedback from the large levels of dopamine in the synapse

amphetamine & methamphetamine

-synthetic agents structurally similar to catecholamine neurotransmitters (dopamine, norepinephrine) -have stimulant properties similar to cocaine

cue-induced drug use

-the increased likelihood of using a drug because factors are present that were also present when the drug was last used -ex. if you always snort cocaine at parties, that craving (dopamine rise) will occur when you step foot into a party, not just after you take cocaine

mechanism of action of alcohol

-works by activating a subset of GABA receptors (GABA is an amino acid and is the neurotransmitter that often inhibits postsynaptically in the brain) -alcohol increases IPSPs in many areas of the brain, reducing the rate of action potentials that are fired -however low doses of alcohol stimulate dopamine pathways and the resulting increase in dopamine --> drunken euphoria

How do drugs affect neural function?

1) acting as agonists 2) acting as antagonists 3) decrease breakdown or prevent reuptake (cocaine blocks dopamine reuptake) 4) alter release (amphetamine increases dopamine and norepinephrine release as well as doing a number of other things) 5) reduce the number of receptors post-synaptically (many tricyclic antidepressants reduce receptors for the catecholamines- dopamine, norepinephrine)

besides just their liver, what other consequences do chronic alcoholics suffer?

1) brain shows gross reductions in the number of synapses in certain regions (ex. cerebellum, frontal lobe). surprisingly, these differences can recover over time if the patient gives up alcohol 2) permanent brain damage 3) tissue degradation

what are the two different ways in which a drug can act as an antagonist?

1) competitive antagonism (receptor blocking)- drug is close enough in composition to attach to the same site the receptor would, but it doesn't open the ion channel. Thus, the neurotransmitter cannot bind to the receptor because the drug is "in the way" 2) noncompetitive antagonist- drug binds to another site on the receptor, so it doesn't stop the neurotransmitter from binding, but it inactivates the channel, so that it will not open when the neurotransmitter binds. Once again, normal transmission is interrupted

what medications can be used to treat drug addiction?

1) drugs for detoxification (benzodiazepines and drugs to help ease withdrawal symptoms) 2) agonists or analogs of the addictive drug (partially activate the same pathways, such as methadone or nicotine patches) 3) antagonists to the addictive drug (block effects of the abused drug but may produce withdrawal symptoms) 4) medications that alter drug metabolism (like Antabuse, which makes drinking produce unpleasant side effects) 5) reward-blocking medications (block positive reward effects of the abused drug but may produce a lack of all pleasurable feelings) 6) immunization (prompts the immune system to remove targeted drugs)

what aspects of neurotransmitters can drugs alter?

1) how neurotransmitters are made 2) how neurotransmitters are released 3) how neurotransmitters bind to receptors 4) how neurotransmitters stay in synapses

what are two biological models of drug dependence?

1) physical dependence model (aka "withdrawal avoidance model"; says abusers use drugs to avoid withdrawal symptoms) 2) positive reward model (says drug use is a behavior controlled by positive rewards, with no disease)

Despite all the differences in mechanism of action of these abused drugs, what is the one common pathway they all share?

all of them stimulate the mesolimbic cortical dopamine pathway and increase dopamine release and action. in fact, this pathway for drug abuse may also be the pathway in the brain for abuse/addiction to other things like sex, shopping, gambling, etc.

why does the craving for nicotine start so soon after a cigarette is smoked?

because nicotine gets into the brain quickly when smoked and because its action on the brain is very short-acting (a few minutes)

however, why would people not suggest that lesions to this area not be done in a smoking cessation clinic?

because then you would lose your conscious control of wanting

antagonists

block action of endogenous neurotransmitter by binding to receptor and preventing endogenous neurotransmitter from binding (curare blocks ACh receptors in the peripheral nervous system)

why might cue-induced drug use be a good way to help stop a craving?

by taking away the cues, the craving then won't be stimulated

what is the most common type of drug effects we will discuss?

cases in which the drug acts at the post-synaptic receptor as either an agonist or antagonist

Look in the textbook for...

figures that show the presynaptic and postsynaptic stages where drugs may affect the brain

cocaine and amphetamine can dramatically _____ blood flow, sometimes causing strokes

increase

so what happens when you lesion the insula in humans?

it decreases incentive motivation such that it is easy to stop smoking cigarettes!

agonists

mimic neurotransmitters by binding to receptor and causing a similar action (nicotine mimics ACh, opium mimics endorphins)

studies done on rats have measured dopamine release in the nucleus accumbens when an animal self administers an abused drug. As the rat self administers cocaine, levels in the nucleus accumbens begins to rise and with each self administered dose of cocaine ___________ dopamine is released

more and more

In humans, the strong cortical control of incentive processing includes what brain regions?

prefrontal and insular cortex

chronic use provokes...?

psychotic symptoms

what happens when a normal neurotransmitter or an agonist drug activates the receptor?

the channel opens and ion flow occurs across the membrane

however, what actually causes withdrawal symptoms?

the down-regulation of dopamine receptors

what causes the depression?

the fact that the small amount of dopamine that normally feels rewarding after a good tasting meal no longer does so because there are fewer receptors

when is this information important?

when considering how drugs may affect neural function ***you should be able to know at least one example of a drug effect at each stage

cessation of use provokes...?

withdrawal symptoms including agitation, drug cravings, and severe depression

can environmental stimuli become associated with the effects of drugs?

yes!

is this same release of dopamine seen when animals self-administer opiates, alcohol, and nicotine?

yes!

can tolerance also be learned to be associated with cues?

yes. for example, if you shoot up heroin in your bathroom late at night, you might grow tolerate to the time of day and location, so if you shoot up mid day in your office you might feel a much larger effect of the same dose because you are not tolerant at that time and place (sometimes how heroin addicts kill themselves in error)