Biopsychology (PSYS 2200) Exam 3

Spring 2026

What is metabolic tolerance?

the body adapts to repeated drug exposure by increasing the rate at which it breaks down and eliminates the substance; reduces the amount of drug that actually reaches its site of action

What other kinds of tolerance are there?

Functional - cellular and conditioned, and cross

What is meant by cross-tolerance?

when chronic exposure to one drug reduces sensitivity to another drug, often within the same class, due to shared neuroadaptive mechanisms

What is sensitization? How might it change the dose-response curve?

Opposite of tolerance; the progressive enhancement/strengthening of a drug’s effect following repeated, intermittent exposure

What is drug withdrawal?

adverse effects of discontinuing drug use

What are some effects of opiates, and how do they differ from the effects of opiate withdrawal?

Opiate effects:

• hypnotic/drowsiness

• constipation

• reduced respiration

• reduced heart rate

withdrawal produces opposite effects

What are the four stages of alcohol withdrawal?

1. tremors, rapid heartbeat, hypertension, sweating, loss of appetite, insomnia (can develop in a few hours)

2. hallucinations (the day or 2 after abstinence)

3. delusions, disorientations, delirium, amnesia

4. seizure

Why is alcohol withdrawal associated with over-excitation in the brain?

chronic alcohol use suppresses excitatory brain activity, forcing the brain to adapt by increasing excitatory signals (glutamate) and decreasing inhibitory signals (GABA) to maintain balace

What evidence suggests that tolerance can be conditioned?

experiments with rats:

CS (environment) + US (morphine) —> unconditioned response (pain reduction)

Conditioning: the CS is paired with the UCS; Testing: CS → how much pain relief does that dose of morphine produce? - done in a neutral environment & paired with morphine

The CS becomes associated with increased pain response (CR); testing phase: CS is paired with saline

results: the rats experienced more symptoms of withdrawal when they received morphine in the test environment compared to in their home cages or no morphine.

Know the 4 classes of drugs that we discussed

stimulants, depressants (sedatives), narcotics, hallucinogens

Stimulants

nicotine - acetylcholine agonist; amphetamine - dopamine agonist; cocaine - dopamine agonist

Depressants (sedatives)

alcohol - GABA agonist and glutamate antagonist; anxiolytic drugs (benzodiazepines - valium - GABA agonist; buspar.- serotonin agonist)

Narcotics

morphine - opiate agonists

Hallucinogens

LSD - serotonin agonist

What are the short term effects of cocaine use?

increased energy, decreased appetite, mental alertness, increased heart rate and blood pressure, constricted blood vessels, increased temperature, dilated pupils

What are the long term effects of cocaine use?

addiction, irritability and mood disturbances, restlessness, paranoia, auditory hallucinations

Medical complications associated with cocaine use

disturbances in heart rhythm, heart attacks, chest pain, respiratory failure, strokes, seizures and headaches, nausea

What is cocaine poisoning? What is it associated with?

the acute, life-threatening physical and behavioral state caused by excessive intake of cocaine, which normal brain neurotransmission. Activating the sympathetic nervous system and causes over-stimulation in the central nervous system.

results in convulsions and respiratory or cardiac arrest; large variability in individual responses make lethal dose difficult to determine; rare unpredictable toxic reactions in some people produces rapid death

What is the cellular effect of cocaine use?

cocaine blocks the reuptake of dopamine; result: dopamine stays in the synapse longer

What did Olds and Milner find?

intercranial self-stimulation (ICSS) - rats would administer bursts of electrical stimulation to their own brains

What are important sites that support ICSS?

hypothalamus, septum, and nucleus accumbens and ventral tegmental area

What is the relationship between dopamine, ICSS and drug abuse?

1. many areas that support ICSS are close to or within the mesolimbic (ventral tegmental area and nucleus accumbens) and mesolimbocortical pathways

2. ICSS produces an increase in DA release in the striatum, particularly the nucleus accumbens

3. dopamine agonists increase ICSS

4. lesions of the mesolimbocortical pathway interfere with ICSS

5. dopamine antagonists blocked the effects of ICSS

6. dopamine agonists produce conditioned place preference

What does microdialysis measure? How?

the release of a neurotransmitter (In vivo)

1. samples are collected through a microdialysis probe stereotaxicaly implanted into an area of interest

2. samples are then analyzed using high pressure liquid chromatography, which separates molecules by molecular weight

What is conditioned place preference?

when repeated drug use occurs in 2 different environments/rooms, during the test, the tendency of a now drug free subject to prefer the drug environment is assessed - more likely to prefer the drug associated room

What is stress?

any deviation of the body from homeostasis

Who was the first person to systematically study stress?

Hans Selye

Explain the entire HPA axis.

the stress response activates multiple systems; cortisol can inhibit the HPA axis (homeostasis)

hypothalamus (corticotropin-releasing factor (CRF)) → anterior pituitary (adrenocorticotropic hormone (ACTH - through blood)) → adrenal cortex → cortisol (type of glucocorticoid)

Explain the endocrine response to stress.

System 1: endocrine; the hypothalamic-pituitary-adrenal Axis (HPA axis)

glucocorticoids (cortisol) in your blood help to release stores of energy from fat - they also inhibit the HPA axis

What are the effects of cortisol?

stimulates the synthesis of glucose, inhibits the uptake of glucose into fat and (some) muscles, stimulates the breakdown of fat, suppress the immune system (anti-inflamatory and immunosuppressive), can affect behaviors (fear)

What is Cushing’s Syndrome caused by?

the increased production of cortisol or by excessive use of cortisol or other steroid hormones; by a tumor of the pituitary gland

What are the different stress response systems?

fight or flight - parasympathetic and sympathetic

What is associated with stress response?

The sympathetic branch of the autonomic nervous system

What are the 4 effects of sympathetic activation that are described on the “system 2” slide?

increased blood flow to muscles, increased heart rate, rise in blood sugar, piloerection (goosebumps)

What is one effect of sympathetic activiation?

To stimulate the release of adrenaline (epinephrine) from the edrenal glands.

Why are the endocrine and autonomic nervous systems catabolic?

they help to mobilize energy resources in the body

What are the behavioral consequences of stress mediated by?

the brain

What did Darwin suggest about emotional expression?

expressions of emotion evolve from behaviors that indicate what an animal might do next

if the signals provided by the behaviors enhance the animal’s ability to survive, they will be retained; opposite messages are revealed through opposite behaviors

What is the difference between the James-Lange theory and the Cannon-Bard theory of emotion?

James-Lange Theory suggested that emotional stimuli activate physiological reactions that are then interpreted as emotional experiences while Cannon-Bard suggested that emotional stimuli simultaneously active reactions and feelings

Explain Ledoux’s idea of a low road and high road of fear responding

two pathways through which the amygdala’s fear responses can be triggered:

a fast “low road” from the thalamus to the amygdala, and a slower “high road” that passes from the thalamus to the neocortex and only then to the amygdala.

• the two paths do not always reach the same conclusions: the low road may respond to a long, thin object as being a dangerous snake - trigger an immediate fear response; slower high road is determining that the object is a harmless stick

How might we observe fear in rodents?

change in heart rate, decreased appetite, increased startle, defecation, decreased pain reactivity, change in motor activity, hypoalgesia

What structure mediates conditioned fear?

the amygdala

what are the Basolateral Complex and central nucleus of the amygdala?

the basolateral complex is where fear conditioning occurs. Neurons in this region that used to only respond to shock will respond to the auditory stimulus after repeated pairing

the central nucleus of the amygdala (CE) is activated by the basolateral complex, and once activated coordinated the fear response

What is manipulated in a learned helplessness experiment?

whether or not the subject (rat) is able to control the termination of the shock (via wheel)

Describe the learned helplessness experimental paradigm.

two groups of rats receive tailshock from the same source, the controllable-shock group can terminate the shock by turning a wheel that is mounted in the front of the chamber. The uncontrollable-shock group receives exactly the same amount of shock, but cannot terminate the shock

dependent variable: impact of stressors; independent variable: feelings of control

two shocks to produce fear; measure freezing for 20 mins; measure escape behavior

What are the effects of learned helplessness?

less aggressive, decrease in social dominance, less eating and drinking, don’t interact much with others, increases in fear-learning, increase in ulcers

What evidence suggests that learned helplessness is a good animal model of depression?

many of the symptoms are comparable, depressed mood, significant weight loss or gain, insomnia or hyper insomnia, psychomotor agitation or retardation, less energy, diminished ability to think/concentrate

learned helplessness is associated with deficits in escape behavior, which is associated with the fight/flight response; associated with increased fear conditioning, and increases indices of anxiety

What are potential flaws of the model?

animals most likely do not experience depression in the way that humans do; learned helplessness is also temporary unless there is repeated exposure to the same stimulus; demonstrates what happens when we feel we have no control over the stressors in our environment

What do Maier and colleagues suggest that Learned helplessness is modeling?

the pathological, behavioral, and neurochemical changes that occur when organisms experience severe, uncontrollable stressors

blocks learned helplessness: destroy the dorsal raphe nucleus (DRN); reduce firing of serotonin neurons in the DRN by injecting specific drugs directly into the DRN

What does uncontrollability do to fight/flight responding? What does it do to fear and anxiety behavior?

causes a decrease in fight/flight responses - increase in fear and anxiety behaviors

What is an autoreceptor?

typically an inhibitory presynaptic receptor that regulates the release of a neurotransmitter; often function as a classic example of negative feedback, a homeostatic mechanism

What evidence suggests that the dorsal raphe nucleus is critical for learned helplessness?

DRN sends serotonin to the amygdala and the dPAG (escape); uncontrollable shock activates neurons that release serotonin in the DRN; more than controllable shock

activation of the DRN is both necessary and sufficient for learned helplessness

What is the dorsal raphe nucleus hypothesis of learned helplessness?

uncontrollable shock overactivates serotonin neurons in the dorsal raphe nucleus; makes the neurons more sensitive to subsequent stimulation, and may also change the way the brain responds to serotonin; produce the behavioral changes associated with learned helplessness

What is the role of the medial prefrontal cortex in learned helplessness?

executive control; inhibits lower brain regions; emotion regulation

In the brain, what might be happening to produce anxiety disorders?

hypothesis: in some anxiety disorders, the amygdala is overactive; either it response too much to a fear-eliciting stimulus, or it responds inappropriately to stimuli that shouldn’t elicit fear

The bed nucleus of the stria terminalis (BNST) and amygdala seem to mediate fear in different situations. Describe some of these situations (i.e. light-enhanced startle, fear-potentiated startle) and which nucleus is critical for each paradigm

Corticotropin-releasing hormone-enhanced startle: CRF increases the amplitude of the acoustic startle reflex, acting as a model for anxiety and stress-related disorders like PTSD; BNST

Light enhanced startle: reflects an anxious state produced by bright light; BNST

Learned helplessness: DRN

How do Walker and Davis explain the difference between fear and anxiety (amygdala versus BNST mediated phenomena)?

the BNST mediates responding as the threatening stimulus becomes longer in duration (moving from phasic to sustained)

differentiate fear and anxiety based on threat duration and neural circuitry - central amygdala mediates rapid phasic fear, and the BNST mediates sustained, long lasting anxiety

How does an allosteric modulator work? How does valium work?

compounds that bind to a different part of the receptor, and make the neurotransmitter better or worse at activating the receptor

many anxiety-reducing drugs work by facilitating the inhibitory actions of GABA - benzodiazepines (valium)

Role of serotonin in anxiety - what is the confusion in the field?

whether a serotonin drug increases or decreases anxiety depends on:

the serotonin receptor subtype targeted (serotonin has more than 18 different receptors); whether the drug is administered chronically; what part of the brain the drug is targeting