ADHD Attention deficit hyperactivity disorder 4.1% American adults age 18 years and older in a given year. 9.0% of American children age 13 to 18 years. Males are 4 times at risk than females
Drug Treatments Stimulant based methylphenidate (Concerta, Metadate, Ritalin, others) dextroamphetamine (Dexedrine) dextroamphetamine-amphetamine (Adderall XR) lisdexamfetamine (Vyvanse) Non-stimulant atomoxetine (Strattera) bupropion (Wellbutrin, others) desipramine (Norpramin). clonidine (Catapres) guanfacine (Intuniv, Tenex)
Non-stimulant ADHD drugs do not have the same side effects as stimulant drugs because They are given at lower doses They act on a different pathway They have the same side effects but side effects are not detectable They have not been studied as long Non-stimulant ADHD drugs do not have the same side effects as stimulant drugs because They are given at lower doses They act on a different pathway They have the same side effects but side effects are not detectable They have not been studied as long
Impulse control brain regions in ADHD frontal cortex basal ganglia thalamus Team Workshop 1. Go to http://www.g2conline.org/2022 and display the 3 brain regions. Link on course website
Stop-signal reaction time task (SSRTT) Sound to single stop going to the light and return to get reward. BL is baseline
Loss of STS or inhibition improves impulse response 39, Xy+0 40, XY Loss of STS or inhibition improves impulse response COUMATE DHEAS intraperitoneal injection and per os (oral)
Why were 40, XY MIF mice used as the control for the SSRTT? C57BL/6 mice were not available C57BL/6 mice cant be used to perform SSRTT To ensure that the mice had 40 chromosomes The have the same genetic background as the 39, Xy+0 mice. They have a mutant STS gene Why were 40, XY MIF mice used as the control for the SSRTT? C57BL/6 mice were not available C57BL/6 mice cant be used to perform SSRTT To ensure that the mice had 40 chromosomes The have a similar genetic background as the 39, Xy+0 mice. They have a mutant STS gene 39, Xy*0 mice have X and Y endjoined that deltes the STS gene. Wildtype 40,XY MF1 mice (Harlan, UK, aged 3–4 months at start of testing) were used in initial work validating the SSRTT; this was necessary as our previous work used C57BL/6 strain mice (Humby et al, 2013). This group of mice were also used for the drug studies. For the genetic study, 39,XY*O and 40,XY mice on a predominantly MF1 is outbred.
Workshop 2: Discuss the reaction steroid sulfatase (STS) catalyzes and how this might be important in ADHD? Testoterone (L) and Estradiol (right)
Workshop 3: Provide a molecular explanation of why coumate is an inhibitor of STS?
Workshop 4: Discuss the following aspects of mouse models and neurological disease. Why are they useful? Why are they problematic?
Remember Before 12 PM of the next class day: go to b.socrative.com/student/login and complete the quiz