Midterm questions

Question 1

Identify the substrates that PKA/G enzymes act on to influence cellular response patterns

Answer 1

• Voltage-gated ion channels
• Ligand-gated ion channels
• Synaptic vesicle proteins
• Enzymes involved in neurotransmitter synthesis
• Proteins that regulate gene transcription

Question 2

Provide a brief account of the structure and function of the blood-brain barrier and identify its relevance for the action and effect of psychotropic drugs

Answer 2

• The blood-brain barrier is the separation between brain capillaries and the brain/cerebrospinal fluid, and it is selectively permeable
• It is relevant because we need to know which drugs readily enter the CNS and which only circulate throughout the rest of the body (this way, drugs can impact the body without having CNS effects)

Question 3

Give a step-by-step account of how the process of neurotransmission works.

Answer 3

1. ) Neurotransmitter is synthesized and then stored in vesicles
2. ) An action potential invades the presynaptic terminal
3. ) Depolarization of presynaptic terminal causes opening of voltage-gated Ca2+ channels
4. ) Influx of Ca2+ ions through channels
5. ) Ca2+ causes vesicles to fuse with presynaptic membrane
6. ) Neurotransmitter is released into synaptic cleft via exocytosis
7. ) Neurotransmitter binds to receptor molecules in postsynaptic membrane
8. ) Opening or closing of postsynaptic channels
9. ) Postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell
10. ) Retrieval of vesicular membrane from plasma membrane

Question 4

For the 5 major divisions of the brain (-cephalons), identify a structure, substructure, and general function for that substructure.

Answer 4

• Myelencephalon (structure: medulla; substructure: area postrema); the area postrema initiates vomiting in response to toxins in the blood
• Metencephalon (structure: pons; substructure: reticular formation); the reticular formation is involved in arousal, attention, sleep, and muscle tone
• Mesencephalon (structure: tegmentum; substructure: periaqueductal gray); the periaqueductal grey is responsible for pain modulation
• Diencephalon (structure: thalamus; substructure: lateral geniculate nucleus); the lateral geniculate nucleus is responsible for receiving visual info from the eyes and projecting it to the primary visual cortex
• Telencephalon (structure: limbic system; substructure: amygdala); the amygdala is involved in emotional responses

Question 5

Explain what the resting membrane potential is and how it is generated.

Answer 5

• The resting membrane potential is the difference in electrical charge inside the cell compared with outside the cell
• It is generated because of selective permeability of the membrane and uneven distribution of ions inside and outside the cell

Question 6

Explain what reliability and validity are in scientific research

Answer 6

• Validity is the extent to which the research is consistent with human subjects
• Reliability refers to the extent to which the tests can be replicated and have the same result

Question 7

Outline the roles of glutamate and GABA in epileptic seizures

Answer 7

• Associations between mutations in the GABA(A) receptor subunits and various types of seizure disorders confirm that normal GABA(A) receptor functioning is required to prevent abnormal increases in brain excitability
• In cases without GABA(A) receptor mutations, dysregulation of the GABAergic systems may still be involved

Question 8

What is long-term potentiation and how does it work?

Answer 8

• Long-term potentiation is a persistent increase in synaptic strength produced by a burst of activity in the presynaptic neuron
• Essentially, the process of increasing the strength of a synapse
• The burst of firing is produced experimentally by a single brief train of electrical stimuli
• Has two types: early and late

Question 9

Explain the rat park experiments and their importance in our understanding of drug addiction and research

Answer 9

• An experiment that involved separating rats into isolated or socialized groups
• They were given an initial choice of morphine laced water, and then only morphine water, and then alternating
• No gender differences, but some difference between groups (isolated rats chose morphine water more often)
• This is important because many human addicts experienced neglect, isolation, etc. prior to drug abuse

Question 10

Explain serotonin’s role in pain modulation, including the roles of specific 5-HT receptor subtypes

Answer 10

LOOK INTO THIS - Serotonin activity along the pathway between the periaqueductal grey and spinal cord tends to inhibit pain signals from periphery through 5HT(1b) and 5HT(3) receptors

Question 11

Summarize norepinephrine’s role in arousal and cognition

Answer 11

• Prefrontal cortex expresses abundance of α1 and α2 receptors; α2 agonists produce an increase in working memory and α1 agonists decreases cognitive performance, indicating a homeostatic balance between these two receptors
• LC neurons fire more rapidly during waking than during sleep; projetions to medial septal nuclei and medial preoptic area
  (hypothalamus) initiate this arousal

Question 12

All drug experiences are a function of dose, set, and setting. Give a brief historical account of drug prohibition and briefly speculate about how these events have influence the set and setting parameters today

Answer 12

• Prior to 1914, ALL drugs were legal, and then in 1914 they could only be prescribed
• Alcohol prohibition came in 1919 and was appealed in 1933 (this is in the US)
• Modern war on drugs began in 1970
• This history helped develop a system for determining drug parameters based on abuse potential and risk potential (for example, some drugs like heroin have a high abuse potential and a high risk potential, with no medical use)

Question 13

Delineate the three dopamine pathways that originate in the midbrain and identify each of their primary functions

Answer 13

• The nigrostriatal pathway originates in the substantial nivea and innervates the caudate-putamen
• The mesolimbic pathway originates in the VTA and innervates various limbic system structures
• The mesocortical pathway originates in the VTA and innervates the cerebral cortex
• The mesolimbic and mesocortical pathways have been implicated in the neural mechanisms underlying drug abuse and schizophrenia

Question 14

How is ethanol metabolized in humans? Outline some of the ethnic and sex differences in this process.

Answer 14

• Once consumed, it is diffused passively into the blood
• 10% absorbed in the stomach, 90% absorbed in the small intestine
• Once in circulation it moves to all tissue, not just the brain
• Liver enzymes break it down at a constant rate
• Majority of it is broken down by enzymes cytochrome P450 and alcohol dehydrogenase (ADH) & acetaldehyde dehydrogenase (ALDH)
• Alcohol has a proportionally greater effect on women (due to body size)
• Some enzymes are more active in men
• B1 deficiency is greater in alcoholic women

Question 15

Outline the neurochemical targets of ethanol. How does it affect various neurotransmitter receptor subtypes?

Answer 15

• Glutamate: has a high affinity for NMDA glutamate receptors; induces memory loss, hyper excitability, excitotoxicity
• GABA: chronic alcohol consumption causes down-regulation of GABA(A) receptors which increases the likelihood of seizures and lowers the effects of benzodiazepine

Question 16

Identify the five factors that influence drug action and give an example influence for each of them

Answer 16

• Routes of administration
• Absorption and distribution
• Binding
• Inactivation
• Excretion

Question 17

Identify all of the ways in which drugs can affect synaptic transmission

Answer 17

• Drug serves as neurotransmitter precursor
• Drug inhibits neurotransmitter synthesis
• Drug prevents storage of neurotransmitter in vesicles
• Drug stimulates release of neurotransmitter
• Drug inhibits release of neurotransmitter
• Drug stimulates postsynaptic receptors
• Drug blocks postsynaptic receptors
• Drug stimulates autoreceptors; inhibits release of neurotransmitter
• Drug blocks autoreceptors; increases release of neurotransmitter
• Drug inhibits neurotransmitter degradation
• Drug blocks reuptake

Question 18

List all of the receptor subtypes (both ionotropic and metabotropic) for acetylcholine

Answer 18

α, β, γ, δ, ε

Question 19

Explain the structure and function of the glutamate NMDA receptor

Answer 19

• It is both ionotropic and metabotropic

- In order to stimulate the NMDA receptor and open its ion channel, both glutamate and glycine are required

Question 20

Describe the neurobiology of drug reinforcement

Answer 20

• Reward circuit: VTA mesolimbic dopaminergic neurons code for reward prediction error; Fibers terminate in NAcc, amygdala, and prefrontal cortex; Amygdala has reciprocal connections with NAcc and BNST; NAcc has subsequent output to the ventral pallidum VP
• Once a reward is paired with a conditioned stimulus, these neurons will fire in response to the conditioned stimulus even before the reward is signalled (reward prediction); Failure of reward after conditioned stimulus leads to decreased activity (prediction error)