Exam 3 Notes: Anabolic Steroids, Hormones, Stress & Memory

EXAM 3 NOTES Lecture 10 Thursday 4/10/2025 Anabolic steroids & sports Lot of ppl in sports used anabolic steroids Lance Armstrong = “king cheat” Therapeutic use of endogenous androgens exception due to testicular cancer Entire Russian team was disqualified AAS Androgens build muscles due to receptors in our ligaments/tendons/muscles Three Main Classes of AAS T or Cyp Most research done in labs on animals are with deca AAS continued Esters and 19-nor Long half lives Stick around a long time 17 alpha Most athletes take this AAS + E Many negative effects are thru E receptor AAS Abuse Increase in use among non-athletes Rate of new abusers more in women than in men Women are using it more for body image than performance People abusing them = supratherapeutic 10x the dose for medical use Stacks You don’t use a single one, you combine a bunch together Intermediate Stack Need aromatase inhibitor to avoid estrogenic effects such as gynecomastia Development of breasts Advance Stack 13 wks of 4 steriods 2 dif aromatase inhibitor Total of 19 weeks Clomid therapy for 4 wks Clomid was used for breast cancer Known as tamoxifen Clomid Putting too much A and E shuts down HPG axis Negative feedback turns it off If we don’t kickstart HPG-axis it will just shut down Binds to E receptors in the brain, limiting amts of E Missing what he said about what happens with LH & FSH** Major side effect of anabolic steroids is shut down of HPG-axis Steroid induced hypogonadism Shrinkage of testes Health Alert Acne on upper back and shoulders = stereotypical of steroid abuse Even though HPG is being shut down so much T in system get increase libido What do women’s breasts get smaller when they use anabolic steroids? Participation Q Medical Complications Death is the biggest outcome Mice given AAS for 2 wks Animals that received 2wks of AAS as adolescents died sig earlier Sig reduction in lifespan Psychiatric Complications of AAS Hyper-mania Depression Cycling between those 2 extremes ^ People get addicted “Roid rage” Increase in violence and aggression Psych at Harvard Don’t need to memorize People that received T showed the changes in the hormonal profile you would expect Increases in T, decrease in LH Went on to test aggression (next slide) Ppl were incredibly aggressive after anabolic injection Not everyone showed the same levels of aggression T is not causing aggression, just potentiating aggression that already exists Side Effects of AAS Anything besides building mass (ex) Lecture 10 Monday 4/21/2025 Hormones and Depression [GET NOTES] Hypothalamus is making enough TRH but anterior pit is not responding to it TRH works alright in depression, but anterior pit isn’t responding as strongly as it should less TSH in response to TRH Some subtypes of depression have an autoimmune component Thyroid high levels of TRH in CSF (3) Refractory patients Haven’t shown response to any standard therapies Combining fluoxetine with T3 = decrease in symptoms Subpopulation of people correlation between mood and concentrations of thyroid hormone Geriatric patients higher T3 level = better overall mood Growth Hormone and Prolactin Normally TRH has no effect on growth hormone Patients who are clinically depressed have increase in growth hormone in response to TRH TRH increased levels of prolactin are produced High levels of TRH in CSF that may lead to production of prolactin Prolactin produced in hypothalamus and released from posterior pituitary Cortisol Glucocorticoids feed back and turn things off (negative feedback) Cortisol Study May be a defect in negative feedback in the HPA axis Testing Feedback Loop 2-3 day test, patients come in and are given a canulate to draw blood (stress of having blood drawn is eliminated) Look at circadian release of cortisol (2 nd day) Night of 2 nd day, injected with dexamethasone (synthetic steroid structured similarly to glucocorticoids should shut down the HPA axis) Study Depressed patients: 2 weird peaks of glucocorticoids Get a suppression when given dexamethasone, but not a sig one, major peak in afternoon for unknown reason Significant reduction of negative feedback in HPA axis with depression High levels of CRH in CSF Get less ACTH in response to CRH in a depressed patient Just like with HPT axis, general blunting which seems to be pituitary response Diseases of HPA axis Diseases associated with adrenal gland Cushing’s: hypercortisolemia Addison’s: hypocortisolemia excessive aldosterone secretion Insufficient mineraloid secretion High levels and low levels of cortisol = associated with depression It may be deviation of homeostatic mean of cortisol in either direction may be the link to depression Estrogens May be estrogenic effect (women suffer more from depression than men) Relationship between estrogen and mood Euthymic = someone not clinically depressed High doses of E to women who are clinically depressed decreases symptoms Peak of depression @ puberty and menopause Major lifetime shift in level of estrogens that may be important Postpartum Depression Specialized subset of depression PPD can last months or years if not treated distinguished from new mothers depression CRH Involvement CRH levels throughout pregnancy higher levels of CRH = higher likelihood of developing PPD Placenta also makes CRH Doesn’t function with normal negative feedback Cortisol stimulates production of CRH in placenta Positive feedback Source of excessive CRH Beta Endorphin Women who showed most severe PPD had elevated ß-endorphin levels in pregnancy Huge increase of ß-endorphin before delivery Labor and delivery is painful and ß = released in response to the pain Building up for maximal levels at time of birth High levels of ß during gestation may be predictive of who may be more susceptible of developing PPD Study Slide 2 (20) Sex of baby may contribute to PPD Seasonal Affect Disorder: Role of 5HT Carb craving what happens when you eat carbs? Hormonally: surge in insulin Insulin takes amino acids out of blood and stores them Does this for all amino acids except tryptophan If big insulin load, only amino acid that is brought into the brain = tryptophan Tryptophan becomes 5HT SAD patients might have less serotonin High levels of 5HT mean low levels of binding for PET tracer Binding Studies SAD may be related to 5HT levels and they are regulated by carb cravings Melatonin 5HT = obligate precursor to melatonin Controls sleep-wake cycle Melatonin is made at night Light interferes with production of melatonin Type of light affects SAD Sun has full wavelength spectrum, regular bulbs do not PMS (all slides) Best treatment for PMS = oral contraceptives Smoothing the hormonal fluctuation hormones fluctuate less Eating Disorders - Anorexia Hormonal profile resembles prepubescent girl Low GnRH and low gonadotropins Low levels of TSH Hormonal affects go away when the woman returns to 5% of what normal bodyweight should be Abnormally low levels of leptin Satiety factor – tells us to stop eating Not a totally sexually dimorphic trait Men who develop anorexia tend to have low levels of T Bulimia During binging phase, decrease in T3/T4 Small study 1/3 rd of women with bulimia had high levels of T Elevated levels of GH Leptin levels are correct for body mass O&A components of EDs Depends on sex of twins F develops ED, likely that F twin develops one, less likely that M twin will develop one M develops ED, greater likelihood of twin F developing an ED than M twin Organizational affect of androgens protective role against EDs Lecture 11 Thursday 4/24/25 A stressor is anything that throws the body out of homeostasis Short term, acute stress = adaptive Lecture 12 & 13 Monday 4/28/2025 [missing first 10 min] Sex Differences (in stress responses) Even not stressed, high levels of corticosterone Stress & Reproduction Semelparous breeder Breeds once and dies (salmon) Semelparous Animals Antechinus – males live 11.5 mos. During mating massive release of glucocorticoids that’s what causes death Exhaustion phase following high levels of glucocorticoids collapses immune system Doesn’t happen if remove adrenal glands PTSD What the individual considers stressful Hippocampus (46) Fewer cells in chronically stressed monkey PTSD study (slide 45) Smaller hypothalamus, the more severe the PTSD Twin PTSD Study Same correlation Not caused by PTSD Smaller hippocampus may have predated PTSD Small hippocampus might predispose to PTSD White Crown Sparrow Study Birds moved to lower branches when weather got bad Implanted birds with GC animals never left the ground GC levels in this species modifies basic life behavior Predictable vs non-predictable stress study Caused peptic ulcers To measure severity of stress size of ulcer Unpredictable stressor has sig larger ulcers Unpredictable stressor = more severe than predictable one Stress & Drug Abuse Rats will press a lever to get injection of GC same way they would press a lever for heroin Stress = number 1 cause of relapsing behavior Sapolsky Paper: GC excess is toxic to the brain, esp hippocampus 3 pieces of evidence: PTSD Cushing’s disease When Cushing’s disease is corrected, hippocampus goes back to normal size reversible effect Depression study The longer the patient was depressed the smaller the hippocampus Patients weren’t depressed when study was done Based on what was known then, they were logical conclusions to come to Yehuda Paper: There is very little evidence that PTSD is related to hypercortisolemia even after a stressful incident PTSD is associated with hypocortisolemia Chronic stress and PTSD ? associated with GC excess Evidence she spoke about is related to short term stressors, Sapolsky’s discussing longer term stressors Could’ve been low levels of GC for a long time Assignment who made the better argument and why? Explain who had the better argument what about 1 argument was convincing and what about the other’s was not Have an opinion with LOGIC for argument Take in things discussed during previous lectures as well as today Lecture 14 – Memory and Learning Monday 4/28/2025 Know the different types of learning and memory and what they are Associative – relationships between stimuli or stimulus & response Fatigue & sensory adaptation In terms of motor task Sensory adaptation Ex: Negative color after-image Fatigue After a while of clicking a pen, get tired Conditioning Classical vs operant Operant Reinforcer = anything that makes a desired behavior more likely to occur Can be positive or negative Extinction Give animal heroin when lever is pressed Take away heroin Animal will press lever but then not receive heroin Animal will stop pressing the lever Behavior can be extinguished for 6mos, give a foot shock, will immediately press the lever Aversive Learning Active & passive avoidance Active engage in behavior to avoid noxious stimulus Passive suppress a behavior to avoid a noxious stimulus Epinephrine Aversive learning stress hormones play a big role One of the first hormones released in response to stress Looking at dose response Know there is a dose response and on either side of optimal dose decreased effectiveness Doesn’t cross blood-brain barrier Time Effect Avoidance learning epinephrine right after training = best response Released within a couple seconds Glucose Hypothesis Cannot wait too long for glucose wait an hour, no effect In general glucose has an effect on memory Alzheimer patients given recall test sometime later given retest and & beforehand given glucose load ( loooots of sugar) Dif significantly better following the glucose load Peripheral-Receptor Hypothesis Epinephrine is activating a receptor that then communicates with the brain beta-adrenergic receptor beta-adrenergic = terminating axons (?) Not one correct answer not mutually exclusive SAA measuring adrenergic activity higher levels of sAA , greater recall of images Diabetes and Insulin Steptozotocin aversive learning and passive aversive learning in diabetic and non-diabetic animals effect of latency on time it took to go to dark compartment increased latency in control and diabetic not as strong in diabetic diabetic animals did not maintain aversive learning for long Glucocorticoids acutely improve learning and memory dose and time dependent manner same pill as plan B Lecture 14? – Learning and Memory Thursday 5/1/2025 Morris Water Maze test of special learning if animal remembers where platform should be, animal will stay in quadrant where platform is found lesion hippocampus = random motion Foot Shock as a Stressor Reference Memory and Working Memory ref mem bait in one arm working mem bait in every arm correlation with errors and circulating levels of corticosterone The Hippocampus apperforin pathway ? give external source of corticosterone, see changes in hippocampus hippocampus is always growing new neurons high and low levels of GC seem to be bad Charts (35) spines are where synapses are made long term potentiation memories are formed chronic stress lose dendritic complexity in CA3 fewer spines, fewer synapses, fewer memories adrenalectomy same affect, dif mechanism Sex Differences in Learning & Memory female rats show much more exploratory behavior than male rats may be hard for them to suppress that activity Radial Arm Maze in first one, males had more correct choices but may not be significant E effect of T Early Life Stress Sexual dimorphism on spatial learning Effects of Estrogens Estrogen increases # spines in CA1 Enhacing LT potentiation Increased density in NDA receptors Wordy Slide Effects on E and spatial learning Effects of E might be slight, and mostly go with spatial learning Effect of Androgens Organizational effect No chance for androgenic organization effect (1 st bullet) Take away organization, lose sexual dimorphism Seasonal Fluctuations in Learning and Memory During mating season, home domain gets larger Compare animals on maze learning in the winter, impaired performance compared to same species during mating season Seasonal Maters In the long day, shorter latency to find platform (find it faster) Take a more direct path to platform Hippocampus gets smaller compared to short and long day Role of ACTH Active avoidance animal has to engage in an activity in order to avoid stimulus Foot shock all over floor so rat climbs pole (unnatural behavior) Take out pituitary and animal takes longer to learn active avoidance Certain amount of ACTH or its not a direct correlation ACTH acts as anti-amnesia Prevents animal for forgetting the association between floor & escape Vasopressin Anti-amnesia Giving more AVP to animal improves memory even more (unlike ACTH) Oxytocin Amnesic makes animals forget Opioids Amnesic affect in some types of learning avoidance enhances trial & error learning though Bedding those that had morphine made bedding association stronger EDC’s SPAs, PFAS, Phthalates