Genes Brain And Behavior Final

Front 1

Define the term open field behavior. Would you expect the ensemble of genes that mediates open field behavior to be similar or different from that which enables startle behavior?

Back 1

The spontaneous activity of a subject within an observation area.

There would be some crossover between open field behavior genes and startle genes. “Animals integrate sensory input even in the open field in the absence of a deliberate external stimulus. A prime example of an extensively-studied locomotor reflex is the startle-response.”

Front 2

Which activity assays are used in mouse models of human psychiatric disorders?

Back 2

Open field, elevated plus-maze, light – dark box.

Front 3

What is prepulse inhibition?

Back 3

Preceding the sudden startle stimulus with a similar low intensity stimulus.

Front 4

What is the neural pathway affected in Parkinson’s disease, and what is the characteristic locomotor phenotype of a patient with Parkinson’s disease?

Back 4

The symptoms of Parkinson’s disease result from loss of dopaminergic cells in the substantia nigra. These dopaminergic cells project to the striatum, and form part of a motor circuit that regulates activity in the ventral nucleus of the thalamus, which in turn sends excitatory input to the motor cortex.

Involuntary tremulus motion, with lessened muscular power, in parts not in action and even when supported, with a propensity to bend the trunk forward, and to pass from walking to a running pace, the essence of intellect being unaffected.

Front 5

Compare and contrast the genetic basis of Huntington’s disease and Parkinson’s disease.

Back 5

In contrast to Huntington’s disease, both genetic and environmental factors determine susceptibility to Parkinson’s disease.

Front 6

Explain the term entrainment. What is the molecular mechanism for entrainment in the Drosophila clock?

Back 6

Synchronization of the endogenous clock with the external light – dark cycle is known as entrainment.

The clock mechanism critically depends on the intracellular transport and turnover of the products encoded by the period and timeless genes, PER and TIM. The genes encoding these transcription factors are themselves regulated by the Clock and Cycle genes. The PER and TIM transcription factors are synthesized from mRNAs in the cytoplasm, where they form dimers. Their cytoplasmic levels start to rise at the beginning of the night. As their protein levels peak in the middle of the night, PER and TIM are translocated into the nucleus, where they shut down the transcription of their own mRNAs by inhibiting the expression of Clock and Cycle. At dawn, light activates the photopigment cryptochrome (CRY), which binds to TIM and tags it for phosphorylation followed by proteolytic degradation. Without TIM, PER also becomes susceptible to phosphorylation and degradation. Following the demise of TIM and PER, the inhibition of the expression of Clock and Cycle is lifted, and the cycle can recommence.

Front 7

What would be the expected phenotype of a timeless null mutant? Would this phenotype be different from a period null mutant?

Back 7

Timeless null mutations generate behavioral arrhythmicity in constant darkness.

Front 8

What would be evolutionary advantages of entrainment to the light – dark cycle?

Back 8

Sleeping at during periods of darkness could help organisms to avoids predators and allows organisms that see better during the day to find food sources.

Front 9

Which structure houses the biological clock in the mammalian brain?

Back 9

Suprachiasmatic nucleus (SCN)

Front 10

What are the characteristic features of rest periods in Drosophila that justify their designation as sleep?

Back 10

Characteristic features of such rest periods include increased arousal threshold and sleep homeostasis, i.e. compensatory resting following sleep deprivation.

Front 11

What parameters of sleep can be quantified in flies? What does the sleep pattern of the minisleep mutant look like?

Back 11

Sleep can be quantified as daytime sleep and nighttime sleep. Total sleep can be determined by adding the durations of the sleep bouts during a 24-hour period.

This mutant, named minisleep (mns), exhibited three times shorter sleep periods than normal flies. It has normal sleep rebound, and is not impaired in performance in behavioral assays such as geotaxis and heat avoidance following sleep-deprivation, as are wild-type flies. However, mns flies have a shorter lifespan.

Front 12

What happens to sleep in flies when rhomboid is overexpressed in the pars intercerebralis of the brain?

Back 12

Increased expression of rhomboid or Spitz in transgenic flies, via the GAL4-UAS binary expression system, or under the control of a heat shock promoter, results in induction of sleep.

Front 13

What are the differences between REM sleep and slow wave sleep?

Back 13

Slow wave sleep is characterized by a drop in blood pressure, a slowing in the rate of breathing, and a reduction in body temperature. During this phase, voluntary muscles are not inhibited; thus, tossing and turning or sleep-walking can occur.

During the REM sleep stage, there are rapid eye movements, and physiological characteristics (e.g. blood pressure) and the EEG pattern are remarkably similar to the awake state. This is the sleep stage during which dreams occur. During REM sleep large muscles are paralyzed and the body is immobile. Respiration and heart rate increase, and penile erections can occur.

Front 14

What is narcolepsy, and how have studies on narcolepsy contributed to our understanding of sleep?

Back 14

People with narcolepsy experience unusual daytime sleepiness, and can manifest uncontrolled periods of REM sleep. Such transitions from wakefulness to REM sleep can be triggered by emotional experiences, most commonly laughing, but also by anger, surprise, excitement, or fear.

A mutation in the Hcrtr2 gene was identified as the culprit for the narcolepsy phenotype. Thus, canine narcolepsy is a fully-penetrant monogenic disorder. However, human narcolepsy, except for familial cases, is thought to be a multigenic condition with sensitivity to the environment (i.e. a quantitative trait).

Front 15

What is the importance of circadian rhythms for the experimental design of studies on behavior?

Back 15

Behavior is expected to decrease during the rest periods promoted by the circadian clock.

Front 16

Explain why altruistic behavior can have fitness benefits.

Back 16

Altruistic behavior that is costly to an individual may provide indirect fitness benefits by increasing the number of copies of its genes in the population through the reproductive success of closely-related relatives.

Front 17

Explain the term “kin selection.”

Back 17

The type of altruistic behavior that benefits close relatives is known as kin selection.

Front 18

What are the purposes of elaborate courtship rituals that precede mating?

Back 18

Courtship rituals enable females to evaluate the quality of competing males.

Front 19

Describe the similarities between the development of birdsong and the acquisition of human language.

Back 19

Similar to birdsong, babbling gradually develops into speech during a critical neonatal period, and the acquisition of language is dependent on auditory input. In fact, development of birdsong is the only animal model for development of human speech, and also serves as a valuable model for neural plasticity during learning.

Front 20

Explain the term “genomic action potential ” in relation to birdsong. Could you envision this term being applied to other behaviors? If so, give an example.

Back 20

The transcription of zenk correlates closely with the initiation of auditory memory formation of a conspecific song, and is transient. This rapid transient expression of zenk has been termed the genomic action potential.

Maybe heat shock proteins being transcribed in response to stress?

Front 21

Moths have evolved volatile pheromones that bring mating partners together from long distances, whereas flies and certain other insects, such as cockroaches, communicate via cuticular pheromones. Discuss the advantages of cuticular versus volatile pheromones in the ecological context of these insects.

Back 21

Volatile pheromones attract mates from greater distances allowing a greater selection. Cuticular pheromones benefit organisms that cannot travel as far and allows them to select mates from within an immediate vicinity.

Front 22

Describe the fitness advantages of accessory gland proteins for both male and female Drosophila .

Back 22

Acp proteins ensure that females only invest the energy to generate oocytes and release eggs when there is sperm available to fertilize them. Since sperm can be stored in the spermatheca of the female reproductive tract, multiple matings give rise to sperm competition . It is, therefore, advantageous for males to render females less receptive to subsequent matings. Some seminal peptides, Acp70A (also known as the “ sex peptide ” ) and Dup99B, induce rejection behavior towards courting males in mated females. This reduced receptivity persists for up to 11 days, during which period the female uses most of the stored sperm to lay eggs. The sex peptide also stimulates feeding behavior in mated females. In addition, seminal fluid contains antimicrobial peptides, which may help protect eggs after oviposition, contributing further to the male’s reproductive success.

Front 23

What is the evidence that regulation of vasopressin expression controls social behavior in voles? What questions does this assertion raise? Is it likely that the vasopressin gene is the only gene responsible for monogamous versus polygamous behavior? What experiments could you design to identify transcriptional differences that may be causal to or associated with propensity towards monogamy or polygamy?

Back 23

A transgenic study that introduced monogamous prairie vole behavior and polygamous montane vole behavior to mice showed that increased vasopressin receptors are linked with monogamous behavior.

It is clear that the oxytocin and vasopressin systems do not act in isolation, but are an integral part of a more complex hormonal network that regulates social behavior.

Front 24

Discuss the relationship between aggressive behavior, mating behavior, and fitness.

Back 24

Access to the most desirable habitats, food resources, and reproductive partners will confer the greatest degree of genetic fitness.

Front 25

What are the major stumbling blocks for identifying genes that mediate aggression in model organisms and in humans?

Back 25

Whereas lobsters provide a simple model system for studying neural mechanisms of aggression, they are not amenable to genetic manipulations.

However, in contrast to crustaceans where high levels of serotonin are associated with increased aggression, in vertebrates low levels of serotonin predispose to elevated aggression.
A major impediment in measuring aggression in Drosophila has been the lack of a rapid and reliable assay that could measure aggression quantitatively.

Front 26

Describe the haploid – diploid mating system of the honey bee.

Back 26

Fertilized eggs that are heterozygous at the csd locus develop into females (workers),
whereas hemizygosity (i.e. a single gene copy) in unfertilized
eggs results in males (drones). Fertilized eggs that are homozygous at the csd locus develop into sterile males, but are removed and eaten by workers in the hive, and therefore, have zero fitness.

Front 27

Give at least five reasons why honey bees are an advantageous model for studying the genetics of social organization.

Back 27

Bees are advantageous insect models because of their large size, which enables neuroanatomical, behavioral, and electrophysiological studies; their haploid – diploid mode of reproduction, which is favorable for genetic studies; and their economic importance as pollinators and honey producers.

Front 28

Compare naturally-occurring variation in feeding behavior and associated genetic polymorphisms between nematodes and fruit flies.

Back 28

Drosophila larvae can be classified either as “sitters ” or “ rovers ” in terms of their
feeding behavior, and these different feeding styles are attributable, at least in part, to a polymorphism in a cyclic GMP-dependent protein kinase, encoded by the foraging gene. C. elegans displays a similar natural variation in feeding behavior. Mutations in the tax2 and tax 4 genes mimic the effects of NPR-1 receptor activation in C. elegans, in that they disrupt social feeding while mutations in the NPR-1 gene increase social feeding.

Front 29

Describe examples of genotype-by-environment interactions in human behavior.

Back 29

Neuropeptide Y is a potent stimulator of hunger and feeding in people, and has also been implicated in anxiety and response to stress.

Front 30

What were the hypotheses and the experimental approach used by Buck and Axel to discover odorant receptors?

Back 30

Buck and Axel hypothesized that odorant receptors would be members of the G-protein superfamily.

They hunted for odorant receptors using PCR amplification with degenerate primers against conserved regions of GPCRs.

Front 31

Why is it generally assumed that the binding pockets for odorants are formed by the transmembrane domains of odorant receptors? Is there experimental evidence for this notion?

Back 31

Analyses of the sequences of odorant receptors revealed the predicted seven transmembrane domains of GPCRs, and showed that sequence diversity was greatest in these transmembrane domains, which presumably form the binding pocket for odorants.

Front 32

What insights regarding the evolution of odorant receptor genes can be obtained by comparing the repertoire of functional odorant receptors in mice and humans?

Back 32

Functional redundancy among odorant receptor genes would allow segregation of pseudogenes in a population, and the complement of pseudogenes and functional alleles may show individual variation. It has been proposed that pseudogenes that contain a stop codon could conceivably undergo a mutation that would restore them to functional receptors, thereby providing a reservoir of “evolvable” functional receptors.

Front 33

What are the perceptual and behavioral consequences for a system that consists of sensory neurons that each express only a single chemoreceptor versus one that consists of sensory neurons that each express multiple chemoreceptors?

Back 33

This strict one-neuron-one-receptor rule ensures that the brain can deduce which receptor was activated by determining which neuron has been activated.

Front 34

In the mammalian olfactory system, olfactory sensory neurons that express the same odorant receptor are not clustered, but distributed in expression zones along the anterior – posterior axis of the olfactory neuroepithelium, while their axons converge on the same glomeruli in the olfactory bulb. How does this organization impact the sensitivity of odorant recognition?

Back 34

This system increases the sensitivity of an organism by increasing the number of receptors that are diversely localized throughout the neuroepithelium.

Front 35

Describe the transgenic method that was employed to study molecular response profiles of odorant receptors in Drosophila.

Back 35

In an ingenious experimental design Carlson and his colleagues made use of a deletion mutant that lacks the Or22a and Or22b genes. In these flies, neurons that would normally express these odorant receptors were silent. This enabled them to generate transgenic odorant receptors that could be expressed under the control of the Or22a promoter in these otherwise silent mutant neurons. This provided an elegant in vivo assay system for a comprehensive characterization of odorant receptor specificities.

Front 36

Describe the genetic transfection approach that was used in rats to elucidate the molecular response profile of an odorant receptor. What have we learned from this study about the breadth of ligand-specificity of odorant receptors? If the odorant receptor were a V1R receptor instead, would you expect a similar, narrower, or broader molecular response profile?

Back 36

When transgenic mice were engineered which express GFP in vomeronasal neurons together with vomeronasal receptors, neural projections to the accessory olfactory bulb visualized a more diffuse pattern than the distinct convergence evident in the main olfactory bulb.

Whereas the main olfactory system and the vomeronasal system were once considered functionally entirely separate chemosensory systems, it is now clear that common odorants can activate vomeronasal neurons, and that vomeronasal
stimuli can activate neurons in the main olfactory epithelium.
A similar response profile would be expected since many of the same ligands can bind to both receptors.

Front 37

What is the strategy that was used to identify the V1R family of putative pheromone receptors?

Back 37

Single-cell PCR and differential hybridization among G α i2 expressing cells resulted in the identification of a new family of chemoreceptors, known as the V1R receptors.

Front 38

Describe the structural differences between V1R and V2R receptors.

Back 38

V1R receptors have seven transmembrane domains, and are expressed only in neurons in the apical zone of the vomeronasal organ.

V2R receptors are structurally distinct from V1R and odorant receptors. They are seven transmembrane domain receptors characterized by a large extracellular N-terminal domain, which resembles metabotropic glutamate receptors and calcium sensing receptors.

Front 39

Describe how transgenic mice that express reporter genes in olfactory or vomeronasal sensory neurons have contributed to elucidating the neural projections of both systems. To what extent do olfactory and vomeronasal projections differ, and what could be the implications of these differences for information processing?

Back 39

Mombaerts and colleagues conducted experiments in which open reading frames of odorant receptors were swapped. They might have predicted that axons would now project to a location that would precisely correspond to the native glomerulus to which axons from cells that usually express the swapped receptor would normally project. This was, however, not the case. The transgenic receptor steered the axons towards the general direction of its native glomerulus, but the placement was not precise. These experiments led to the conclusion that additional factors other than the odorant receptor are needed to generate precise projections. Such factors are likely to include differentially-expressed components of the extracellular matrix and their interactions with axon guidance molecules. For example, knock-out mice which were deficient in the extracellular matrix components ephrin A and ephrin B showed distortions in the chemotopic map, suggesting that ephrin gradients may play a role in determining connectivity.

Consequently, glomeruli in the accessory olfactory bulb are smaller and less
well-defined than their counterparts in the main olfactory bulb. The projection pattern in the accessory olfactory bulb suggest that decoding of chemosensory information, which occurs in cortex in the olfactory system, happens earlier in the vomeronasal projection, perhaps already at the level of the first synapse in the accessory olfactory bulb.

Front 40

What is the advantage of using transgenic calcium-sensitive reporters to visualize glomerular activation in the olfactory bulb, as compared to conventional application of calcium-sensitive fluorescent dyes? What are the limitations of real-time fluorescent imaging studies in the olfactory system?

Back 40

The ability to genetically-tag neurons that express a defined odorant receptor with a fluorescent reporter enabled the identification of ligands for such receptors, as ligand-activated calcium signals could be directly associated with a fluorescent glomerulus.

Front 41

What conclusion regarding the olfactory system could be drawn from studies on mice that were cloned from a single olfactory neuron?

Back 41

The functional organization of their olfactory system was indistinguishable from that of normal mice, with olfactory neurons each expressing a unique different odorant receptor rather than all expressing the same receptor; thus, the choice of odorant receptor does not involve irreversible alterations in genome structure.

Front 42

Describe the genetic approaches that were used to identify the human taste receptor for phenylthiocarbamide.

Back 42

The PTC taste phenotype segregates as a nearly Mendelian trait, and was mapped to a region on chromosome 7q. This chromosomal region contains a T2r receptor gene, and association analyses in which taster and non-taster phenotypes were associated with distinct haplotypes identified this gene, which encodes the T2R38 receptor, as the source of the observed phenotypic variation for PTC taste ability.

Front 43

Discuss the labeled line versus the cross-fiber pattern theories for taste recognition, and indicate how results from studies with knock-out mice affect these opposing theories.

Back 43

For many years, researchers in the taste field found themselves divided into two camps, those that believed that taste modalities were separate and hardwired to taste perceptions via segregated neural mechanisms (the labeled line theory ), and those that believed that individual taste cells could respond to multiple types of tastants and that the relative activity across the population of taste cells gives rise to the gustatory perception (the cross-fiber pattern theory ). Although this debate still lingers, and the controversy is by no means resolved, evidence derived in the last decade from studies on transgenic mice increasingly favors the labeled line hypothesis.

Front 44

What is the proposed function of odorant-binding proteins, and how could their presence or absence affect odorant sensitivity?

Back 44

Odorant binding proteins (Obps) are soluble proteins, which are secreted by nasal glands and have been postulated to facilitate partitioning and transport of hydrophobic odorants in the aqueous mucus that covers the olfactory neuroepithelium. Protecting odorants from degradation or a role in the removal of odorants has also been postulated for these proteins.

Front 45

What is known about the recognition of carbon dioxide in Drosophila? How could understanding olfaction in the malaria mosquito Anopheles gambiae be exploited for the development of new disease control strategies?

Back 45

Chemosensory information about CO 2 in Drosophila, when sensed by gustatory neurons, is relayed to a specialized region of the suboesophageal ganglion and an attractant response is elicited. However, volatile CO 2 is sensed by olfactory neurons in the antenna, which project to a single glomerulus in the antennal lobe, designated glomerulus V.

Blood-feeding mosquitoes have orthologs of both Gr21a and Gr63a which are expressed in neurons in their maxillary palps, which serve as CO 2 sensors. Understanding the mechanisms by which blood-feeding insect disease vectors, such as the malaria mosquito Anopheles gambiae, locate their hosts may lead to the development of disease-prevention strategies.

Front 46

What is the difference between massed learning and spaced learning? Which procedure is more effective in generating long-term memory?

Back 46

When different learning paradigms for the formation of long-term memories are compared in a variety of model organisms, one invariably finds that repeated training sessions separated by time intervals (spaced learning) are far more effective for the consolidation of long-term memory than a single continuous intensive training session (massed learning)

Front 47

What are the advantages and limitations of studies on learning and memory in Aplysia?

Back 47

Their neurons have unmyelinated axons that are large, to increase propagation speed in the absence of salutatory conduction; because of their larger size, these axons are easier to impale with electrodes. Furthermore, marine invertebrates have simpler nervous systems. In many species, such as the sea slug Aplysia californica , they form defined neural circuits in which individual neurons can readily be identified.

Front 48

Describe how mutations have been used to identify the different phases of memory consolidation in Drosophila.

Back 48

Dunce mutants are defective in normal short-term memory formation, and can form memories only briefly. The dunce gene is expressed in the mushroom bodies, which have been implicated as the integrative centers in associative learning in the fly brain.

Rutabaga mutants can only acquire rapidly-decaying memories.

Amnesiac mutants show near-normal memory retention immediately after a single training session, and again about seven hours later. Interestingly, however, between these time points, memory retention in amnesiac mutants is lower than normal, indicating that the amn mutation disrupts memory at a stage intermediate between initial learning and memory consolidation.

Another mutant, Radish, specifically abolishes anesthesia-resistant memory, while long-term memory remains intact.

A final mutant, Tequila, prevents the formation of long term memory.

Front 49

Which cellular pathways that regulate gene expression during memory formation have been identified in all three models of Aplysia , Drosophila , and mice?

Back 49

The formation of long-term memories depends on phosphorylation reactions through cyclic AMP-dependent protein kinase and MAP kinases that result in activation of transcription factors, such as CREB. Activation of CREB regulates gene expression, and gives rise to long-term synaptic modifications. These cellular pathways are evolutionarily-conserved.

Front 50

What is the role of phosphorylation and dephosphorylation in acquisition of memory in the hippocampus?

Back 50

Phosphorylation and dephosphorylation of histones by transcription factors mediate changes in the epigenome that can increase the activity at a synapse.

Front 51

Describe the conditioned fear learning paradigm.

Back 51

Fear conditioning is a behavioral paradigm in which organisms learn to predict aversive events by pairing an aversive stimulus with a neutral one.

Front 52

Discuss neurogenetic methods that can be used to investigate the role of the mushroom bodies in learning in Drosophila.

Back 52

Use of RNAi and the GeneSwitch system showed that suppression of Tequila prevents the formation of LT memory in the mushroom bodies.

Ablation of the mushroom bodies during development eliminates learning, even though animals are still able to sense, and respond to, stimuli.

Front 53

What is a Hebbian synapse? Describe the role of synaptic coincidence-detection in mediating long-term potentiation.

Back 53

Synapses that rely upon both conditioned and unconditioned stimuli. Cells that fire together, wire together!

If all of the conditions required to activate the NMDA receptor are not fulfilled long-term potentiation will not occur.

Front 54

Describe two behavioral paradigms that are commonly used to assay spatial memory in mice and rats.

Back 54

Morris water maze and the radial arms maze.

Front 55

What is dyslexia? How strong is the experimental support for the DYX1C1 gene as a candidate dyslexia gene?

Back 55

Individuals with dyslexia find it difficult to acquire and consolidate written information. Phonological deficiencies, that is, the inability to process speech sounds and recognition of words and their meaning, are also common.

The strongest evidence for association between the DYX1C1 gene and dyslexia rests only on the four affected individuals from the original family study.

Front 56

What appears to be a common functional theme among dyslexia genes which have thus far been identified?

Back 56

All of them relate to cell migration, cell adhesion, and axon growth, which can explain some of the cortical malformations seen in some cases of dyslexia, establishes them as interesting candidate genes.

Front 57

What are common problems encountered in human genetic studies aimed at identifying alleles that contribute to learning disorders?

Back 57

This is likely because these disorders rely on a large number of genes that have a relatively small impact on their own. Additionally, the mutations in these genes are not always present in all cases.

Front 58

What is the genetic basis for Fragile X syndrome?

Back 58

Fragile X syndrome, attributed to a trinucleotide expansion in the FMR1 gene.

Front 59

If heritability for performance on the Wechsler IQ test is high, does that mean per se that there are genes of major effect that contribute to intelligence? Explain.

Back 59

It appears from studies to date that the diverse manifestations of phenotypes,
which we collectively refer to as “intelligence, ” are regulated by many genes of small effect with likely few, if any, genes of large effect.

Front 60

Which is the best-established gene with risk alleles for late-onset Alzheimer’s disease?

Back 60

An allele of ApoE has been implicated in late-onset Alzheimer’s disease.

Front 61

What are the criteria for animal models for Alzheimer’s disease, and what genetic strategies can be used to generate such models? What behavioral assays would be appropriate to monitor neurodegeneration?

Back 61

For such models to be useful, they must recapitulate the behavioral and neurodegenerative features of the disease.

Performance in the Morris water maze and conditioned avoidance learning paradigm.

Front 62

What are the hallmarks of addiction?

Back 62

Hallmarks of addiction are dependence and withdrawal. Dependence can be either physical, psychological, or both.

Front 63

How does habitual eating of bacon and eggs for breakfast differ from addiction? Or does it?

Back 63

A habit becomes an addiction when cessation of the action results in withdrawals and the activity is harmful to your well-being.

Front 64

Why would genetic risk for addiction to gambling be accompanied by genetic predilection for substance abuse?

Back 64

Neurobiological studies have implicated the same motivation
and reward pathways in gambling as in alcohol and drug addiction.

Front 65

How can one disentangle environmental and genetic contributions to alcohol abuse in people?

Back 65

By using twin, adoption and family studies to trace the heritability of the disorder.

Front 66

What have we learned about alcohol sensitivity and tolerance from candidate gene approaches and whole genome transcriptional profiling studies in Drosophila?

Back 66

One of the first mutants identified by using the candidate gene approach was named cheapdate and showed increased sensitivity to alcohol and is an allele of amnesiac which is implicated in memory formation.

Whole genome transcriptional profiling studies have shown that altered regulation of intermediary metabolism may accompany the development of tolerance in is reminiscent of metabolic changes that occur in heavy drinkers who are prone to develop fatty liver syndrome, a reversible condition characterized by the accumulation of fat in the liver.

Front 67

A small set of candidate genes has been the target for association studies on addiction to several different substances. What are these genes and why have they been the focus for these studies?

Back 67

One polymorphism of the dopamine 2 receptor, known as the Taq1A allele, has been identified in some studies as a risk factor and several other neurotransmitter-receptor genes have also been implicated, most notably the GABA receptor.

Front 68

What have we learned about cocaine addiction from dopamine transporter knock-out mice?

Back 68

Surprisingly, however, mice in which the dopamine transporter has been deleted are hyperactive, but still show conditioned place preference when exposed to cocaine, indicatingthat compensatory mechanisms can mediate the drug’s reward effects.

Front 69

Imagine that you are a scientist interested in identifying genetic variants associated with compulsive gambling. What experimental and conceptual problems would you have to consider in your experimental design?

Back 69

Gambling isn't available as easily everywhere which adds a complex environmental component to experimental design.

Front 70

Is the metabolism of addictive substances an important factor in developing physiological dependence? If so, give examples.

Back 70

Isoforms of the alcohol dehydrogenase gene have been correlated with alcohol use in human populations. Enzymes that regulate the bioconversion of other addictive substances, such as cytochrome P450 2A6, which metabolizes nicotine, also represent important factors in determining addictive or adverse health effects of drugs.

Front 71

What behavioral assays are used to measure analgesia in mice, and how do mice in which the μ -opioid receptor gene has been deleted respond in these assays?

Back 71

Morphine-induced analgesia was measured by the time and stimulus threshold it takes for the animal to flick its tail or jump up from a hotplate when exposed to a painful temperature. The tail flick or hotplate responses of wild-type mice were attenuated by morphine, but morphine had no effect on the knock-out mice. Similarly, the knock-out animals did not show a conditioned place preference when given a choice between a chamber in which they had been previously exposed to morphine versus an environment without morphine administration.

Front 72

Several controlled substances have medical applications. Give two examples.

Back 72

Opioids and Cocaine

Front 73

What are the advantages and limitations of genome wide association studies?

Back 73

Precise assessment of phenotypes is often challenging in human populations, and recruitment of addicted individuals and ethnic diversity of the study population further complicate genetic association studies.