PMCOL 343: Animal Models for Drug Development

Comprehensive practice vocabulary flashcards covering behavioral models, psychopharmacology assays, rodent genetics, disease models, and cutting-edge genetic approaches from PMCOL 343 Lectures 1a, 2, and 3.

Automata (Descartes)

René Descartes's conceptualization that animal behavior is non-conscious and can be completely reduced to simple, mechanical reflex actions without a mind.

Rational Soul (Descartes)

In Cartesian philosophy, the uniquely human attribute capable of abstract thought and true reasoning, which Descartes argued is entirely absent in animals.

Homologous Structures (Darwin)

Anatomical similarities shared between humans and lower animals that Charles Darwin and Alfred Wallace cited as physical evidence that humans evolved from animals.

Instincts vs. Habits (Darwin)

The evolutionary framework proposed by Charles Darwin stating that animals and humans inherit instincts, whereas humans uniquely develop habits that are learned rather than inherited.

Sir Charles Sherrington (1900 view)

The physiological perspective positing that non-human animals act entirely without a mind and provide no valid evidence of subjective thought, feelings, or perception.

Wilhelm Wundt (1911 view)

The psychological perspective proposing that rudimentary animal sensations, such as fear, directly parallel foundational human sensations.

Ivan Pavlov (1897 view)

The experimental observation that conditioned dogs salivate upon the perception of incoming food, demonstrating evidence of perception, memory, and organized thought in animals.

Animal Model

An experimental test system that attempts to imitate specific aspects of a human clinical condition to screen potential therapeutics and evaluate underlying biological substrates.

McKinney's Four Criteria (1977)

The foundational criteria used to validate an animal model: similarity of inducing conditions, similarity of the induced behavioral state, similarity of underlying neurobiological mechanisms, and similarity of clinically effective treatments.

Opioid Dependence Model

A rodent model established by administering morphine through a subcutaneous slow-release capsule, inducing physical dependence and reward behavior followed by precipitated withdrawal.

Naloxone

An opioid receptor antagonist administered to precipitate acute withdrawal syndromes in morphine-dependent laboratory animals.

Clonidine

An $\alpha$-adrenergic agonist used in humans and rodents to alleviate opioid withdrawal symptoms, serving as a positive treatment control in dependence models.

BU224

An experimental imidazoline receptor antagonist evaluated in opioid dependence models for its efficacy against withdrawal signs such as wet dog shakes, mouth movements, and diarrhea.

Wild Norway Rat

The feral rodent species common in Europe that spread to North America on ships by 1775, historically known as a biting economic hazard and disease vector via fleas.

Wistar Rat

An albino laboratory rat strain established by Donaldson at the Wistar Institute in 1906, characterized by poor visual acuity.

Long-Evans Strain

A hooded rat strain with black eyes and good vision created circa 1915 by Drs. Long and Evans by breeding female Wistars with a wild male trapped in a campus creek.

Sprague-Dawley Rat

A widely used albino rat strain developed by Mr. Dawley and Miss Sprague by mating a hooded rat to a female Wistar, selected for rapid growth, vigor, and calm temperament despite poor vision.

Independent Variable

The variable manipulated by the experimenter, which in behavioral pharmacology commonly corresponds to the specific drug type or dosage administered.

Dependent Variable

The observed and measured outcome in an experiment, such as a quantified animal behavioral response, that changes as a function of the independent variable.

Double-Blind Study

An experimental protocol wherein neither the subjects nor the experimenters know the condition or treatment assignment, minimizing both experimenter bias and placebo effects.

Three-Group Design

An experimental framework evaluating therapeutic efficacy by comparing an experimental drug group, a placebo/vehicle control group, and an established reference drug group.

Learned Helplessness

A behavioral phenomenon described by Seligman (1975) wherein animals exposed to inescapable, uncontrollable aversive events show reduced motivation to initiate escape responses.

Porsolt Forced Swim Test

A behavioral despair screening assay developed by Dr. Roger Porsolt in which rodent immobility, swimming, and climbing behaviors are monitored in a cylinder of water over a timed period.

Fluoxetine (Prozac)

A selective serotonin reuptake inhibitor (SSRI) that reduces immobility and selectively increases swimming behavior in the Porsolt forced swim test.

Reboxetine (Edronax)

A noradrenaline reuptake inhibitor (NRI) antidepressant that reduces immobility and selectively increases climbing behavior in the Porsolt forced swim test.

Tail Suspension Test

A behavioral despair model in which mice are suspended upside-down by their tails from a force transducer to measure immobility time and righting effort.

Elevated Plus Maze

An unconditioned conflict test for anxiety based on rodent aversion to open, elevated spaces compared to closed, protected arms, scored via entry counts and duration.

Lorazepam

A benzodiazepine anxiolytic that increases total time spent on the open arms and decreases the latency to first open-arm entry in the elevated plus maze.

Yohimbine

An $\alpha_2$-adrenergic antagonist stimulant that produces anxiogenic effects, significantly increasing open-arm entry latency and reducing open-arm time in the elevated plus maze.

Vogel Conflict Test

A fast-screening anxiety assay (Vogel et al., 1971) in which water-deprived rodents receive mild electrical shocks while licking water, where anxiolytics restore punished drinking behavior.

Defensive Burying

An ethologically valid anxiety paradigm where an animal pushes bedding toward an electrified shock probe following initial contact and shock delivery.

Y-Maze

A rapid behavioral apparatus designed to evaluate spatial working memory by tracking spontaneous continuous alternations between three arms (labeled A, B, and C).

Morris Water Maze (MWM)

A complex spatial navigation task in which rodents placed in milk-colored water at $22^\circ\text{C}$ use distal spatial cues to locate a submerged, hidden escape platform within $90\text{ seconds}$.

Fmr1 Gene Deletion

The genetic mutation in Fragile X model mice that causes impaired spatial learning and delayed cognitive performance in the Morris water maze, especially during reversal trials.

Reversal Trial (MWM)

A modified Morris water maze trial where the submerged platform is moved to an alternate quadrant, evaluating cognitive flexibility and new spatial learning.

Hippocampal Dependency (MWM)

The physiological requirement of an intact hippocampus for spatial memory acquisition in the Morris water maze, demonstrated by severe performance deficits following hippocampal but not neocortical lesions.

Donepezil (Aricept)

A cholinesterase inhibitor designed to prevent the enzymatic degradation of acetylcholine, enhancing cognitive and memory performance in humans and animal models.

Memantine (Namenda)

An NMDA receptor-regulating therapeutic that modulates glutamate neurotransmission involved in the processing, storage, and retrieval of memory.

Radial Arm Maze (RAM)

An eight-armed cognitive apparatus used to dissociate spatial reference memory from working memory by evaluating rodents retrieval of food pellets from specific arms.

Working Memory Error (RAM)

An operational error in the radial arm maze defined as an animal re-entering an arm from which it has already consumed the food pellet during that single trial.

Reference Memory Error (RAM)

An operational error in the radial arm maze defined as an animal entering an arm that was baited during the initial training phase but is permanently unbaited during testing.

Three-Chamber Social Interaction Test

A behavioral paradigm that evaluates sociability and preference for social novelty by timing an experimental rodent's exploration of a stranger mouse versus an empty wire cage or a novel stranger.

Corticotropin-Releasing Factor (CRF)

A stress-related neuropeptide that elicits robust anxiogenic-like responses, resulting in a marked dose-dependent reduction of rodent social interaction.

Habituation (Startle Reflex)

The progressive attenuation of the acoustic or tactile startle reflex following repeated exposure to an identical startling stimulus.

Prepulse Inhibition (PPI)

The physiological attenuation of the startle reflex observed when a startling acoustic pulse is preceded by a weak, non-startling prepulse stimulus.

Apomorphine Model of Deficient PPI

A translational rodent model of schizophrenia wherein apomorphine, a non-selective dopamine receptor agonist, disrupts sensorimotor gating, a defect reversed by antipsychotics.

Middle Cerebral Artery Occlusion (MCAO)

An experimental model of focal ischemic stroke induced by temporary or permanent occlusion of the middle cerebral artery, triggering downstream apoptosis and necrosis.

TTC Stain (2,3,5-Triphenyltetrazolium Chloride)

A histochemical viability dye that turns metabolically active, redox-functional brain tissue deep red while leaving non-viable ischemic, necrotic infarct areas pale or white.

TUNEL Stain

A histochemical staining method that detects DNA fragmentation in tissue sections, selectively identifying apoptotic cells in ischemic brain damage.

Edaravone (MCI-186)

A synthetic free radical scavenger that exerts neuroprotective effects against brain damage and infarct progression in rodent models of permanent focal cerebral ischemia.

Experimental Autoimmune Encephalomyelitis (EAE)

An animal model of multiple sclerosis induced by immunization with central nervous system myelin peptides, generating T-cell-mediated neuroinflammation and demyelination.

MOG35-55

A synthetic myelin oligodendrocyte glycoprotein peptide used as a specific encephalitogenic antigen to induce experimental autoimmune encephalomyelitis in susceptible C57BL/6 mice.

EAE Clinical Score

A graded rating scale used to track motor impairment, progressive weakness, and ascending hind limb paralysis in rodents, which typically manifest $10\text{ to }14\text{ days}$ post-immunization.

Cre-Lox System

A site-specific genetic recombination technology utilizing Cre recombinase enzyme to excise or invert target DNA sequences positioned between directional loxP recognition sites.

Floxed KCNMA1

A transgenic mouse strain possessing loxP sites flanking the KCNMA1 gene (encoding the BK potassium channel alpha subunit), allowing cell-type-specific gene ablation upon Cre exposure.

AdVil Promoter (AdVillin)

A tissue-specific gene promoter that restricts Cre recombinase expression exclusively to sensory neurons located within dorsal root ganglia (DRG).

CRISPR-Cas9

A eukaryotic gene-editing technology derived from the prokaryotic adaptive immune system, utilizing single guide RNA to target Cas9 endonuclease to generate site-specific double-strand breaks.

Protospacer Adjacent Motif (PAM)

A short, conserved DNA sequence (specifically $5'\text{-NGG-}3'$ for Streptococcus pyogenes Cas9) located immediately adjacent to target genomic DNA, essential for Cas9 recognition and cleavage.

Channelrhodopsin-2 (ChR2)

An algal-derived light-gated cation channel that permits $Na^+$ and $Ca^{2+}$ influx to excite neurons and trigger action potentials in response to blue light illumination.

Halorhodopsin (NpHR)

A light-driven inward chloride pump ($Cl^-$) that hyperpolarizes and inhibits neuronal firing when stimulated by yellow light.