quiz 3

lectures 9, 10, 11

what are some types of unconditioned behavioral tests? what do they measure?

• open field test (spontaneous motor activity & anxiety)

• elevated plus maze (anxiety)

• the incline plane test (muscle tone or weakness)

• the hot plate test (analgesia w drugs) -observations of various stereotyped motor behaviors

what is classical conditioning? who discovered it?

learned association between two stimuli leads to reflexive action (Pavlov & dogs)

• unconditioned stimulus: food
• conditioned stimulus: ringing of bell
• reflexive action: salivation/drooling

what is operant conditioning? who developed it?

learning the relationship between a behavior and a consequence (Skinner's Box)

• the rat learns the association between pressing a lever and receiving a reinforced (e.g. food) or a punisher (e.g. foot shock)
• this behavior will occur w greater frequency if reinforced and will quickly extinguish if reinforcer is removed or behavior is punished

what is drug reinforcement?

the strengthening of behavior that leads to drug consumption

what is drug reward?

the positive experience associated with the drug (subjective)

why do we study drug use on animals?

the rewarding properties derived from these studies are a strong indicator of its potential for misuse and dependence in humans

what are the two types of drug reward/reinforcement in animal models for SUD?

conditioned place preference test (CPP) intravenous drug self-administration (IVSA)

how can we tell if a drug is rewarding with animals?

if the animal will lever press for infusions of the drug or prefer to spend time in the chamber that has the drug

what does the conditioned place preference test measure?

measures the rewarding effects of objects, substances, or experiences

• relies on a conditioned association between drug effect and environment

how do we know if the drug is rewarding or aversive during a CPP?

• if the drug is rewarding, the animal spends much more time in the environment associated with the drug
• if the drug is aversive, the animal prefers the environment not associated with the drug
• where they decide to go is the reflexive action

what is the belief behind operant conditioning?

behavioral responses are emitted without any apparent stimulus

• re-occurrence of behavior depends upon the consequences of the behavior

what does reinforcing vs. punishing consequences do?

• reinforcing consequences increase the likelihood of the behavior occurring again
• pushing consequences decrease the likelihood of the behavior occurring again

what types of stimuli are there?

positive: stimulus is added negative: stimulus is removed

what does IVSA measure?

it measures the addictive/misuse potential in humans and the reinforcing effect of drugs

what did IVSA discover?

animals will readily self-administer drugs like cocaine, meth, heroin, but won't self-administer aspirin, anti-depressants or anti-psychotics

why will animals self-administer drugs with a high potential for misuse ?

they tend to produce positive "rewarding" effects in humans and thus have a high potential for misuse

what are reinforcement schedules?

how often and under what circumstances does the animal receive the reinforcer

what is the fixed ratio schedule?

there is an active and inactive lever and the number of times an animal has to lever press to receive a drug infusion doesn't change throughout the experiment

what does a fixed ratio schedule help determine?

misuse liability through comparing active vs. inactive lever presses

what measures the reinforcing effects of the drug?

preferential increases in responding on the active lever over the inactive lever

what is the progressive ratio schedule?

the animal must work to receive drug infusions on a schedule that becomes increasingly more demanding over time

what is the breaking point

when the behavioral demand exceed's the drug's reinforcement value

• the harder the animal is willing to work, the higher the break point, and thus the greater the drug's potential for misuse in humans

what does the electrical self-stimulation method allow for?

animals can self-administer a weak electrical current into discrete brain areas via an indueling electrode, causing local NT release

what is the mesocorticolimbic pathway?

it is involved in reward/pleasure, motivation, reinforcement learning, and addiction

what is the mesocortical pathway?

the ventral tegmental area (VTA) to the prefrontal cortex (PFC)

what is the mesolimbic pathway?

ventral tegmental area (VTA) to nucleus accumbens (NAc)

• dopamine is released here in response to natural and artificial rewards (observed during drug use, sexual behavior, and food consumption)

what is optogenetics?

using light to selectively activate brain regions and cell subtypes

what ion channels are activated by blue light?

channelrhodopsins, which are cations

what ion channels are activated by yellow light

harlorhodopsins, which are anions

what did optogenetics discover?

blue light activates dopamine neurons and the greater the level of light stimulation, the more often mice lever pressed to activate the light

how do we study the effects of drugs in humans?

in human behavior through many types of tests

what is the most powerful human behavior test?

subjective effects (self report)

• people self report the effects drugs have on them

what behavior test quantifies it?

measuring performance:

• motor skills
• perceptual (auditory, visual, etc.)
• driving: stimulants create narrowed focus
• memory

what tests use people to study human behavior?

clinical trials

what are the phases of clinical trials?

• phase 1: small group to test safety (dose and toxicity)
• phase 2: larger group to test effectiveness and safety
• phase 3: larger group to confirm effectiveness
• phase 4: post-marketing (long-term safety)

how long do new drugs take to develop?

~15 years (FDA approval)

how do pharmaceutical companies protect and profit from their investment?

they patent their drug so no other company can sell it for 20 years

what is drug tolerance?

a diminished response to a drug of a given dosage after repeated exposure to that drug and increasingly larger doses are required to obtain the same magnitude of the effect (reduced potency)

what is cross-tolerance?

tolerance that extends to other drugs (usually of the same class) even when the other drug has never been used

what are some characteristics of tolerance?

• it is reversible when drug use stops
• it is dependent on dose, frequency, and the drug-taking enviro
• it may occur rapidly, after long periods of use, or never
• not all effects of a drug show the same degree of tolerance
• several diff mechanisms explain multiple forms of tolerance

what is acute drug tolerance?

tolerance to a drug that develops in a single administration

• the subjective effect of the drug is greater during absorption than elimination, even though the blood level is the same

what kind of tolerance is pharmacokinetic tolerance?

metabolic, the repeated use of a drug reduces the amount of the drug available at the target tissue

what happens to a frequent drinkers enzymes?

they begin to produce more enzymes to break down alcohol, which increases their tolerance

What kind of tolerance is pharmacodynamic?

tolerance arises from adjustments made in the brain to compensate for an effect caused by continued presence/use of a psychoactive drug

where do the adjustments during pharmacodynamic tolerance come from?

neuronal homeostatic processes that work to maintain a specific "set point"

• changes compensate for continued presence of a psychoactive drug in order to restore balance to the system

how does receptor down-regulation work?

agnostic receptors overexcite the neuron, so there is a decrease in sensitivity of the post-synaptic neuron because there are fewer receptors for the drug to act on

how does receptor up-regulation work?

antagonist receptors decrease activity in the neuron, so target neurons up-regulate the number of receptors, increasing sensitivity so the NT can get its message across