Week six

Question 1

Nervous System Agents

Answer 1

A wide variety of both natural and artificial chemicals capable of altering information processing and signaling mechanisms within and among neurons
NSA effects are typically dose-dependent (i.e., effects vary with the amount of the agent administered (aka dose level)*
Some NSAs can cause reversible changes to neural function (e.g., alcohol, chlorpromazine) being diluted via metabolic action
Some NSAs can cause permanent changes to neural function (e.g., botulinum toxin, MPTP) through damaging action to neural tissue
Some NSAs can act as a “neuroprotectant” – resulting in the recovery or regeneration of affected neuron function
* There are a variety of dose-dependent relationships, including controversial ones, such as hormesis

Question 2

PSYCHOPHARMACOLOGY

Answer 2

Study that utilizes knowledge and skill from chemistry and neuroscience.

Question 3

Neurotoxicity

Answer 3

Most nervous system agents are neurotoxic at some dose level
Behavioural toxicology: subdiscipline of psychopharmacology that studies the effects of toxic levels of NS Agents on behaviour, cognition, emotion and consciousness…
MedWatch: USFDA medical product safety reporting program for health professionals, patients and consumers…

Question 4

Characterizing Drug Action: Pharmacodynamics and Pharmacokinetics

Answer 4

Pharmacodynamics: Nervous System Agents have different effects and mechanisms of action upon nervous tissue sites depending on
the route of delivery,
the amount taken (the dose, purity, etc.),
the time-course of NS Agent action and movement throughout the body (affected by metabolism, etc.) – called the drug’s pharmacokinetics…

Question 5

Effects of Nervous System Agents

Answer 5

Therapeutic Effects – the intended consequences on the NS of a nervous system agent (aka a drug ‘treatment’)
Side Effects – Effects that occur but are not related to the purpose of taking the drug
Contraindications – negative side effects
Placebo effects – Therapeutic effects not attributable to drug action (tends to work best on subjective symptoms such as pain)

Question 6

The Dose Response

Answer 6

The functional relationship between the drug dose level & some dependent measure of drug’s effect

Question 7

Dose Response Descriptors:

Answer 7

Median Effective Dose (e.g., ED50) the minimum dose level that produces a measurable therapeutic effect in 50% of the study sample

Question 8

The Dose Response

Answer 8

Median Toxic dose (e.g., TD50) the minimum dose level that produces a measurable toxicity effect in 50% of the study sample

Question 9

The Dose Response

Answer 9

Median Lethal dose (e.g., LD50), the minimum dose level that kills 50% of the study sample

Question 10

Operational Definitions of Dose Response

Answer 10

“Subjective” Effects:
Experiential changes reported by patient (e.g., changes in attention, mood, perception, etc.)

Question 11

Operational Definitions of Dose Response

Answer 11

Behavioural Effects:
Changes in patient’s behaviour (indicating effects on memory, decision making, communication, reaction time, fine motor coordination, speech, etc.)

Question 12

Operational Definitions of Dose Response

Answer 12

Physiological Effects:
Changes to vegetative physiologic functions such as breathing rate, heart rate, body temperature, appetite, tremor, sleep levels, etc.

Question 13

The Dose Response Curve

Answer 13

Typically represented as a curve on an x-y plot with dose on the x-axis and the dependent measure (normalized response) on the y axis
The shape of the curve is sigmoidal…
ED50 (aka median Effective Dose) = the lowest dose that proves effective for 50% of the participants in the study sample

Question 14

An Example of an Experimental Dose-Response Measure:

Prepulse Inhibition of the Acoustic Startle Response

Answer 14

An unpredictable, brief (but LOUD) white noise burst presented through headphones typically elicits a strong acoustic startle response (including, among other things, an eye blink). The eye blink’s latency and amplitude can be quantified by measuring the electrical activity oftheorbicularis oculimuscle on the face with electrodes (see right eye, below).

Question 15

Prepulse Inhibition Deficit

Answer 15

A deficit of prepulse inhibition occurs when the presence of the prepulse fails to reduce the magnitude of the acoustic startle response to the subsequent LOUD noise burst.
Prepulse inhibition deficit has been observed in patients with diagnoses related to abnormalities of automatic sensorimotor gating associated with early attentional mechanisms in the brain (e.g., in patients diagnosed with ADHD or schizophrenia).

Question 16

Prepulse Inhibition: An Example of an Experimental Dose-Response Measure:

Answer 16

Drugs developed to treat attentional deficits might, therefore, be expected to restore the prepulse inhibition of the acoustic startle response to ‘typical’ levels at some (aka “effective”) drug dosage (e.g. taken as ED50 in a study sample).

Question 17

Mechanisms of CNS Agent Action: Agonists and Antagonists.

There are two general ways that nervous system agents have an effect on neural communication

Answer 17

Agonists: increase efficiency of within or between neural signaling

Question 18

Mechanisms of CNS Agent Action: Agonists and Antagonists

There are two general ways that nervous system agents have an effect on neural communication

Answer 18

Antagonists: decrease the efficiency of within or between neural signaling

Question 19

AGONISTS

Answer 19

Two types:
Direct-acting agonists: NS Agents that directly bind to the membrane channels or postsynaptic receptors. Examples of direct-binding agonist drugs include dopamine, apomorphine, and nicotine.

Indirect-acting agonists: agonists that enhance the neurotransmitter actions by stimulating neurotransmitters’ release E.g. cocaine.

Question 20

ANTAGONISTS

Answer 20

Two types:
Direct-acting Antagonist – block cell membrane ion channels or block NT from binding to the postsynaptic receptors.
A common example of a drug belonging to this category is Atropine.
Indirect-acting Antagonist – inhibit release or production of NT
An example of this type of drug is Reserpine.

Question 21

NS Agents Can Affect Signaling Within Neurons: Channel blockers

Answer 21

are antagonistic NS Agents that reduce the flow of ions across the cell membrane, affecting the dynamics of the membrane potential of cells, including neurons.
There are specific channel blockers for all major ions affecting signaling within neurons (Na+,K+,Cl- and Ca++)

Question 22

Natural agents

Answer 22

(E.g., Tetrodotoxin, found in various organs of the puffer fish*) is a Na+ channel blocker that completely inhibits the creation of action potentials by binding to the voltage-gated channels on axon membranes (recall the voltage-gated Na+ channels form the rising phase of the action potential)

Question 23

Pharmaceutical channel blockers

Answer 23

act by inhibiting ion movement through neuron membranes (dependent on dose), altering the rate of depolarization, reducing neuron ‘excitability’ and action potential conduction velocity. E.g., Lidocain (a local anesthetic), Phenytoin and Oxcarbazepine (anticonvulsants) .

Question 24

Channel openers (aka channel activators)

Answer 24

are agonistic NS Agents that facilitate the flow of ions across the cell membrane, affecting the dynamics of the membrane potential of cells, including neurons.
There are specific channel openers for all major ions affecting signaling within neurons (Na+,K+,Cl- and Ca++)

Question 25

Natural agents

Answer 25

: (E.g., Maitotoxin, a calcium channel agonist found in a dinoflagellate Gambierdiscus toxicus, binds to the plasma membrane Ca++ pump and turns it into an ion channel...

Question 26

Pharmaceutical channel openers

Answer 26

act by facilitating ion movement through neuron membranes (dependent on dose), altering the rate of depolarization, increasing neuron ‘excitability’ and action potential conduction velocity. E.g.,. Potassium channel opener (Retigabine --anticonvulsant) (Flupirtine – analgesic/ muscle relaxant, anticonvulsant)

Question 27

Way # 1: Drug substitutes for one of the precursor chemicals involved in production of NT

Answer 27

NET EFFECT: AGONIST Locus of effect: in the presynaptic processes leading to NT production Example drug: L-DOPA: a precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) collectively known as catecholamines.

Question 28

Way # 2: Drug inhibits production of NT by a precursor chemical

Answer 28

NET EFFECT: ANTAGONIST Locus of effect: in the chemistry of the presynaptic processes leading to NT production Example drug: Fenclonine, also known as para-chlorophenylalanine (PCPA), acts as a selective and irreversible inhibitor of tryptophan hydroxylase -- an enzyme in the biosynthesis of serotonin

Question 29

Way # 3: Drug Prevents Storage of NT in Vesicles

Answer 29

NET EFFECT: ANTAGONIST Locus of effect: presynaptic processes in cytoplasm Example drug: Reserpine irreversibly blocks the monoamine transporter which normally transports free monoamine NTs in the presynaptic nerve terminal into presynaptic vesicles for subsequent release into the synaptic cleft. Unprotected NT is metabolized by Monoamine Oxidase in the cytoplasm and consequently never binds to the postsynaptic receptors

Question 30

Way # 4: Drug stimulates release of NT in vesicles

Answer 30

NET EFFECT: AGONIST Locus of effect: Presynaptic membrane Example drug: Latrotoxin (black widow spider venom) – acts presynaptically to release NT (e.g., acetylcholine) from sensory and motor neurons

Question 31

Way # 5: Drug Inhibits Release of NT

Answer 31

NET EFFECT: ANTAGONIST Locus of effect: processes preceding the release of NT at the presynaptic membrane Example drug: Botulinum toxin – prevents vesicles containing the NT acetylcholine from docking/fusing with the interior surface of the presynaptic membrane. In inhibiting acetylcholine release, nerve impulses are blocked, causing the flaccid paralysis of muscles

Question 32

Way # 6: Drug stimulates postsynaptic receptors

Answer 32

NET EFFECT: AGONIST Locus of effect: on the postsynaptic receptors Example drug: nicotine – binds to nicotinic acetylcholine receptors that initiates a reaction resulting in the release of several neurotransmitters affect mood, decrease food intake and bodyweight (by influencing the hypothalamic melanocortin system), decreases muscle tone, etc.

Question 33

Way # 7: Drug blocks postsynaptic receptors

Answer 33

NET EFFECT: ANTAGONIST Locus of effect: acetylcholine receptors on the post-synaptic membrane Example drug: curare --reversibly inhibits the nicotinic acetylcholine receptor, a subtype of ACH receptor found at the neuromuscular junction Example drug: atropine (“belladonna”) –

Question 34

Way # 8: Drug stimulates autoreceptor action

Answer 34

NET EFFECT: ANTAGONIST Locus of effect: in the presynaptic processes leading to NT production Example drug: apomorphine – binds to autoreceptors resulting in the inhibition of dopamine production in the `presynaptic bouton…

Question 35

Way # 9: Drug blocks autoreceptor action

Answer 35

NET EFFECT: AGONIST Locus of effect: in the presynaptic processes leading to NT production Example drug: clonidine -- inhibits autoreceptor activity which, in turn, results in an increase in the synthesis of NT (e.g., norepinephrine)

Question 36

Way # 10: Drug blocks reuptake of NT in synapse

Answer 36

NET EFFECT: AGONIST Locus of effect: in the synapse Example drug: cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons, leaving more NT in the synapse to bind to the receptors of the postsynaptic membrane

Question 37

Way # 11: Drug inactivates acetylcholinesterase

Answer 37

NET EFFECT: AGONIST Locus of effect: in the synapse Example drug: Physostigmine acts by interfering with the metabolism of acetylcholine by reversibly inhibiting the action of acetylcholinesterase, the enzyme responsible for the breakdown of acetylcholine in the synaptic cleft of the neuromuscular junction. Thus, it indirectly stimulates both nicotinic and muscarinic acetylcholine receptors

Question 38

Delivery of Nervous System Agents

Answer 38

Oral route (most convenient, safest) Direct injection into nervous tissue (most effective) Intramuscular injection Inhalation (fewer ‘barriers’ on way to brain) Transdermal (patch, oral mucosa) Intravenous injection Intrathecal injection Anal suppositories (for infants or when patient cannot hold down food)

Question 39

All Central Nervous System Agents Must Pass the Blood-Brain Barrier

Answer 39

Inside the meninges the junctions of endothelial cells that make up brain capillaries are ‘tight’ due to their mechanical coverage by the end feet of astrocytes. Tight endothelial junctions only allow small, non-ionized (i.e., fat-soluble) molecules to pass through the capillary wall Active transport (e.g., ATPase, sodium-potassium pump) can convey larger molecules, (glucose, amino acids, etc.)

Question 40

Three ‘gaps’ in the Blood-Brain Barrier

Answer 40

Pituitary Gland-- of the hypothalamus receives blood-borne hormones and, itself, secretes hormones into the blood for circulation to ‘target’ organs Area Postrema -- region that triggers vomiting response to blood-borne toxins Pineal Gland -- affected by cycling hormones (resulting in neural control over diurnal rhythms, etc.)

Question 41

Through the Blood Brain Barrier

Answer 41

Cell infiltration: through the tight junctions Uptake by neurons projecting through the BBB (eg. Nasal epithelium, motor nuclei of cranial nerves, ventral horn neurons, etc.) Uptake by neurons projecting to areas with a weak or compromised BBB

Question 42

CNS Agents are mainly small molecules...

Answer 42

small molecule drugs have been by far the most successful class of CNS therapeutics Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of the system affects large volumes of the brain, called volume transmission. Major neurotransmitter systems include the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system, and the cholinergic system, among others.

Question 43

Four Activating Systems That use NTs created in the Brainstem

Answer 43

Each is associated with a small molecule NT (i.e., that can easily cross the BBB) Each NT activates a specific type of receptor on the post-synaptic membrane of neurons Each activating system is associated with a different set of structures and functions. The suffix “ergic” – means ‘driven by’ dopaminergic -- system driven by dopamine serotonergic – system driven by serotonin, etc.

Question 44

Cholinergic System

Answer 44

Acetylcholine generated in nuclei in the midbrain and basal forebrain Participates in maintaining attention and waking EEG patterns Involved in maintaining neuronal excitability – thought to be a key element in memory mechanisms Loss of cholinergic neurons associated with Alzheimer’s disease

Question 45

Dopaminergic System

Answer 45

Dopamine generated in nuclei in two distinct pathways: Nigrostriatal dopaminergic system: plays a role in coordinating movement Mesolimbic dopaminergic system: plays a role in reinforcement and reward Abnormal dopaminergic system function is associated with Parkinson’s Disease and Schizophrenia, loss of impulse control, addictive behaviours, etc.

Question 46

Noradrenergic System

Answer 46

Norepinephrine (noradrenalin) generated in the locus coeruleus: Maintenance of emotional tone Decreased NE activity is thought to be related to depression, hyperactivity and ADHD Increased NE activity is thought to be related to mania

Question 47

Serotonergic System

Answer 47

Produced in the Raphe nuceli in the brainstem Loss of serotonin regulation associated with OCD, tics and schizophrenia, sleep apnea, etc. Decreased serotonin associated with depression (possibly a different type from that associated with Noradrenaline)

Question 48

Types of CNS Agents: Analgesics

Answer 48

Nervous system agents that reduce pain at dose levels that don’t alter consciousness Common classes of analgesics include: Salicylates e.g., aspirin, sodium salicylate Contraindications: gastric irritation, deafness Nonsalicylate, nonsteroidal anti-inflammatory drugs (aka NSAIDS) -- e.g., ibuprofen Contraindications: nausea, vomiting, headache, blurred vision, dizziness, drowsiness Narcotic analgesics (aka opioids) –e.g., oxycodone, codeine, morphine Contraindications: addictive

Question 49

Anorexiants

Answer 49

Drugs used to treat obesity in patients who have not lost weight by dieting... Typically stimulate the satiety mechanisms of the hypothalamus and limbic system (e.g., phentermine – and other amphetamine derivatives)

Question 50

Anorexiants

Answer 50

Drugs used to treat obesity in patients who have not lost weight by dieting... Typically stimulate the satiety mechanisms of the hypothalamus and limbic system (e.g., phentermine – and other amphetamine derivatives)

Question 51

Anticonvulsants

Answer 51

Used to treat epileptic seizures by blocking sodium channels or enhancing the inhibitory action of gamma aminobutyric acid (GABA) A wide variety of anticonvulsant drugs have been developed to treat seizures. (e.g., Carbamazepine (trade name: Tegretol))

Question 52

Antidepressants

Answer 52

Used in the treatment of major depressive disorder (MDD) Often used in combination with other drugs directed at alleviation of symptoms Typically aimed at potentiation of seratonergic and/or adrenergic pathways e.g., selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (trade name Prozac)

Question 53

Antiemetic/antivertigo agents

Answer 53

Inhibit vomiting and nausea by blocking serotonin receptors in the CNS and GI tract and dopamine and histamine receptors in the brainstem Used to treat motion sickness, the side effects of opioid and general anesthetics and chemotherapy used to treat cancer. Histamine receptor antagonists (aka antihistamines) e.g., dimenhydrinate (trade name Gravol)

Question 54

Antiparkinsonism agents

Answer 54

Used to treat Parkinson’s disease, caused by the loss of dopamine, an important neurotransmitter associated with the basal ganglia. Antiparkinson agents replace dopamine or mimic dopamine’s effects on dopaminergic receptors in the postsynaptic membrane or prevent dopamine from being broken down chemically Examples of antiparkinsonism agents include carbidopa / levodopa (trade name Sinemet)

Question 55

Antipsychotics (aka Neuroleptics or major tranquilizers)

Answer 55

Used to treat positive symptoms of schizophrenia (including hallucinations, delusions, paranoia and disordered thought) First generation (aka “typical” antipsychotics, discovered in the 1940’s) block D2(dopamine) receptors Second-generation (aka ”atypical” antipsychotics, discovered in the 1960’s) block D2 receptors but for a shorter time period and ALSO block serotonin receptors. Examples: 1st gen: Chlorpromazine, 2nd gen: Risperidone

Question 56

Axiolytics, sedatives and hypnotics (aka ‘minor tranquilizers’)

Answer 56

Used to treat chronic anxiety as well as panic disorders by enhancing the action of GABA (the most common inhibitory neurotransmitter in the CNS) Examples of Benzodiazepines: diazepam (trade name Valium) clonazepam (trade name Klonopin) alprazolam (trade name Xanax)

Question 57

Cholinergics

Answer 57

Substances that modulate the effects of acetylcholine (aka Ach, a major neurotransmitter involved in learning and memory in the CNS and the main neurotransmitter of the parasympathetic division of the peripheral nervous system – and the first neurotransmitter to be discovered)

Question 58

Cholinergics

Answer 58

and the first neurotransmitter to be discovered) Ach is used to treat Alzheimer’s disease, and modulated parasympathetic action (e.g., dilate the pupil (atropine), constrict the pupil (pilocarpine)

Question 59

Cholinergics

Answer 59

Cholinesterase inhibitors (aka anti-cholinesterase) prevents acetylcholine breakdown by the enzyme cholinesterase in the synapse, leaving more Ach available for neurotransmission.

Question 60

General anesthetics

Answer 60

Compounds that produce reversible effects including immobility, loss of consciousness, amnesia, analgesia and a reduction in autonomic activity, typically restricted to surgical procedures (intravenous injections typically initiate anesthesia and inhalants maintain it) The mechanism of action of general anesthetics is to inhibit CNS exitatory neurotransmission and/or activating inhibitory neural mechanisms. Median Minimal Alveolar Concentration: the lowest dose level of an inhalant anesthetic that prevents 50% of the study sample from responding to surgical incision...

Question 61

Muscle relaxants

Answer 61

Chemicals that block the signaling action at the neuromuscular junction (e.g. d-tubocurarine chloride which acts as an antagonist for the nicotinic Ach receptor) Muscle relaxants are employed as part of "balanced" general anesthesia: a triad of barbiturate hypnosis, light inhalational anesthesia and muscle relaxation drugs

Question 62

Psychedelics

Answer 62

A subclass of psychoactive drugs that cause hallucinations and altered states of consciousness, changes in perception, cognition and emotion Commonly used for religious rites, recreation and, increasingly, psychotherapeutic treatment Hypothesized mechanism of action as a “Neuromodulator” – altering the effectiveness of Various neurotransmitter systems Examples: mescaline, LSD, psilocybin

Question 63

Psychostimulants

Answer 63

Substances that enhance neurotransmission by potentiating catecholaminergic and serotonergic pathways OR by inhibiting negative feedback through action on autoreceptors Examples include: amphetamines, caffeine, ephedrine, methylphenidate nicotine, cocaine, pseudoephedrine

Question 64

VMAT2 inhibitors

Answer 64

VMAT2 is a protein in the neuron membrane that transports monoamine neurotransmitters (e.g., dopamine, serotonin, histamine and norepinephrine) from the cytosol into synaptic vesicles

Question 65

VMAT2 inhibitors

Answer 65

VMAT2 function is also required for vesicular release of GABA

Question 66

VMAT2 inhibitors

Answer 66

Patients with cocaine-induced mood disorders have lowered VMAT2 immunoreactivity (a measure of the amount of VMAT2 protein in neurons)

Question 67

Hormones

Answer 67

Molecules produced by glands and “broadcast” (e.g., by the circulatory system) Hormones bind to receptors located in distant ‘target’ organs which regulate and control physiological and, through them, behavioural activities Water-soluble hormones are readily transported in the blood Lipid-soluble hormones must bond to carrier plasma glycoproteins

Question 68

Hormones have various effects on the body

Answer 68

- Stimulation or inhibition of growth - Regulation of circadian rhythms - Mood - Induction or supression of cell death (apoptosis) - Activation or inhibition of immune system - Regulation of metabolism - Preparation of body for mating, fighting, etc. - Preparation of body for new phase of life - Control of aspects of the reproductive cycle - Hunger regulation - Sexual arousal

Question 69

Mechanisms of Hormonal Secretion

Answer 69

Endocrine -- hormones secreted directly into the bloodstream via ‘fenestrated’ capillaries, borne to target tissues in blood Exocrine – hormones secreted via ducts Paracrine – hormones diffuse through the interstitial space to nearby target tissues Pheromone – hormones broadcast into the environment

Question 70

Neuroendocrine System

Answer 70

The Central Nervous System regulates body physiology through neuroendocrine integration, involving the hypothalamus, that: Maintains homeostasis (temperature, blood pressure, tissue osmolarity, etc.) Regulates metabolism through control of eating and drinking behaviour Regulates reproduction Energy utilization achieved through the controlled secretion of hormones from the pituitary gland There are four major neuroendocrine systems

Question 71

The Hypothalamic-Pituitary-Adrenal (HPA) Axis

Answer 71

The paraventricular nucleus of the hypothalamus causes release of two peptides: vasopressin and corticotropin-releasing hormone, which stimulate the secretion of adrenocorticotropic hormone (ACTH) in the anterior pituitary lobe. ACTH is dumped into the blood supply whereby it is carried to the adrenal glands, stimulating the release of cortisol affecting: Regulation of digestion Immune system activity Mood and emotion Sexuality Energy storage and expenditure Mechanisms mediating the body’s response to stressors

Question 72

The Hypothalamic-Pituitary Gonadal (HPG) Axis

Answer 72

development and regulation of the reproductive and immune systems  The hypothalamus releases gonadotropin-releasing hormone that passes through the hypophyseal* portal system to stimulate the anterior pituitary, causing the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH), both of which activate the ovaries in females to produce estrogen and regulate the menstrual cycle and which also stimulate the testes in males to produce testosterone and promote spermatogenesis.

Question 73

The Hypothalamic-Neurohypophyseal System

Answer 73

Hypothalamic axonal connections to the posterior pituitary (aka neurohypophysis) A site for secretion of the neurohypophyseal hormones (vasopressin and oxytocin) into the blood supply. Involved in uterine contractions during birthing and lactation as well as the regulation of water retention via activation of kidneys and vascular arterioles

Question 74

6 steps of Hormonal signaling

Answer 74

1. Biosynthesis of a particular hormone in a particular tissue 2. Hormonal storage and secretion 3. Transport of the hormone to the target cells 4. Recognition of the hormone by an associated cell membrane or intracellular receptor protein 5. Relay and amplification of the received hormonal signal via transduction or binding 6. Breakdown of the hormone (note that these steps are similar to the signaling via neurotransmitter action)

Question 75

Compare and Contrast: Hormones & Neurotransmitters

Answer 75

Hormones can signal over longer distances and longer time scales than NTs Hormonal signals are “omnibus” –i.e., they can travel ‘all over’, rather than being restricted to pre-existing axonal tracts Neural signals are MUCH faster (milliseconds) Hormones are much slower (secs, min, hrs.) Neurotransmission is “all or none” whereas hormonal signaling is graded (dependent upon concentration)

Question 76

3-stage Hierarchical Control by Hormones

Answer 76

Stage 1: Sensory (e.g., light or touch) and/or cognitive activity (e.g., thoughts or emotions) result in neurohormones produced in the hypothalamus that enter the pituitary gland (hypophysis).

Question 77

3-stage Hierarchical Control by Hormones

Answer 77

Stage 2: These hormones stimulate the pituitary gland to secrete secondary, ‘releasing’ hormones, into the circulatory system where they travel throughout the body.

Question 78

3-stage Hierarchical Control by Hormones

Answer 78

Stage: 3: These circulating hormones act upon various target organs in the body as well as brain structures (the latter as feedback for controlling further hormone release).

Question 79

3 Broad Classes of Hormones

Answer 79

Lipid-derived Hormones (e.g., testosterone, cortisol) derived from cholesterol; enter target cells to affect DNA controlling protein production

Question 80

3 Broad Classes of Hormones

Answer 80

Amino Acid - Derived Hormones small molecules derived from tyrosine and tryptophan (e.g. epinephrine, synthesized in the adrenals)

Question 81

3 Broad Classes of Hormones

Answer 81

Peptide Hormones (insulin, oxytocin, growth hormones, endorphins) manufactured by cellular DNA; stored in vesicles and bind to metabotropic receptors on the cell membrane generating a 2nd messenger

Question 82

3 Broad Classes of Hormones

Answer 82

Amino-acid and Peptide Hormones are water-soluble and insoluble in lipids. Therefore, they cannot pass through cell membranes so their receptors must be located on the outer surface of their target neurons (similar to NT receptors located on the postsynaptic membrane)

Question 83

Hormone Functions

Answer 83

Homeostasis: Regulate physiological systems such as water content in the blood, metabolite burden, digestion, etc. as well as circadian rhythms Melatonin is a hormone secreted by the pineal gland in the brain. It helps regulate other hormones and maintains the body's circadian rhythm. (The circadian rhythm is an internal ~24-hour "clock" that plays a critical role in determining when we fall asleep and when we wake up. When it is dark, your body produces more melatonin. Melatonin is also produced as a pharmaceutical to treat sleep disorders and to minimize effects of jet lag, etc. It also has anxiolytic properties and is used in treating anxiety before and after surgery...

Question 84

Hormone Functions, Cont’d

Answer 84

Reproduction: Regulate reproductive functions (eg., lactation, menstrual control, sexual development) Estrogen: primary female sex hormone; responsible for development and regulation of the female reproductive system and secondary sex characteristics Testosterone: affects gender development and expression (both somatic and behavioural) Progesterone: an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species

Question 85

Hormone Functions, Cont’d

Answer 85

Stress response: Secretion of glucocorticoids affect protein and carbohydrate metabolism; blood sugar levels, etc. Important in autonomic responses to emergency ‘fight or flight’ situations. Two mechanisms: one ‘faster’ and one ‘slower’: Faster response: hypothalamus to spinal cord to activate the sympathetic division of the ANS, which stimulates the adrenal gland, releasing epinephrine (adrenaline) into the circulatory system which activates body cells, endocrine glands and brain tissues Slower response: hypothalamus releases Corticotrophin Releasing Factor into the pituitary. Pituitary releases Adreno-Cortico-Tropic-Hormone (ACTH) onto the adrenal gland, causing the adrenal gland to release cortisol into the circulatory system which activates body cells endocrine glands and brain tissues

Question 86

Stopping the Stress Response

Answer 86

Shutting down the stress response reduces the metabolic demands (important for energy conservation) Hippocampus regulates production of cortisol via a negative feedback loop -- has a normally high density of cortisol receptors that, when stimulated, inhibit production of cortisol via inhibition at the level of the hypothalamus Prolonged exposure to stress results in prolonged exposure of the hippocampal neurons to cortisol, which in turn causes destruction of (or reduces sensitivity in) hippocampal neurons. This, in turn, reduces the brain’s ability to shut off cortisol secretion. Implicated in Post-traumatic Stress Disorder (PTSD)