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What makes drugs addictive? Drug tolerance – occurs because the body tries to maintain homeostasis in presence of high neurotransmitter levels What makes drugs addictive? Repeated drug use causes elevated dopamine Body decreases # dopamine receptors, dopamine prod’n “Down regulation” Dopamine receptors Normal Abuser Study showing down regulation Repeated doses of morphine reduce # of dendrites in dopamine neurons What makes drugs addictive? Now a higher dose is necessary for ‘high’ Normal ‘happy’ increases in dopamine can’t stimulate pleasure bc the pleasure center is badly altered Endocrine system Hormones are transported by the blood, but only cause responses in target cells Endocrine functions Regulation of growth and development Homeostasis - ex: salt/water balance, stress, metabolism Reproduction Types of hormones Amines use tyrosine (epinephrine and norepinephrine) Peptides (oxytocin, vasopressin, GH, insulin, TSH) Both types are water soluable Types of hormones Steroids - from cholesterol (adrenal cortex, testis, ovary and placenta). Hydrophobic, transported by proteins How do hormones signal cells? Steroid and thyroid hormones activate genes Diffuse freely into and out of cells Receptor proteins are in cytoplasm. Hormone binds and moves inside nucleus How do hormones signal cells? Peptide hormones utilize a 2nd messenger mechanism Target cells have specific receptor for hormone on cell surface, which triggers 2nd messenger Comparing the two systems Nervous system - signals sent via specific “wiring” rapid, precise responses Endocrine system - specificity is at the receiving end overall body responses, effect may take hours Fig. 5-1, p. 108 Nervous system - divided into central and peripheral regions Somatic nerves innervate skeletal muscles Autonomic nerves innervate internal organs Fig. 5-2, p. 109 Neuroglia Most CNS cells are glial cells They provide structure and maintain interneurons in the CNS Are capable of dividing, even in nuclei of adulthood glial cells neuron Astrocytes: hold neurons together establish a blood-brain barrier w/capillaries repair brain injuries breakdown some neurotransmitters take up excess K+ from the brain ECF Microglia are the immune defense of the CNS Oligodendrocytes form myelin sheaths around axons Ependymal cells line the internal cavities of the CNS. Question: How does multiple sclerosis form? Multiple sclerosis – immune system targets oligodendrocytes, causing degeneration of myelin in CNS Cranial meninges Dura mater Arachnoid Pia mater Scalp Skull Arachnoid mater Subarachnoid space of brain Brain Ventricles Right lateral ventricle Left lateral ventricle Third ventricle Fourth ventricle Cerebral spinal fluid (CSF) provides almost neutral balance for brain (it “floats”) cushions and nourishes brain produced by tissue in ventricles CSF produced in ventricles and resorbed in venus sinus Hydrocephalus Meningitis Meningitis: infection, inflammation of meninges - viral or bacterial. Bacterial infections are quite serious and can result in encephalitis, brain damage, death. Why is it often difficult to deliver drugs to the brain? Blood brain barrier Exists at capillaries that serve the brain Capillaries have tight junctions Normal capillary Lipid-soluble substances Astrocyte processes Water-lined pore BBB capillary Carrier-mediated transport Lipid-soluble substances Tight junction What molecules pass through the blood brain barrier? Lipid soluble vs. water soluble Brain infections are generally rare, but harder to fight when established (antibodies can’t pass) Meningitis How can drugs pass through the blood brain barrier? The BBB makes it difficult for drug treatments to enter brain Not everything can be small, lipid soluble Via nanotechnology, engineered molecules may carry treatments otherwise water soluble (posterior) gray matter white matter (anterior) cortex Table Cerebral 5.3 (1) Page 144 Cerebral cortex Cerebrum Basal nuclei Basal nuclei Cerebrum Cerebral cortex is highly convoluted, outer layer of gray matter. It covers an inner core of white matter. An inner core of basal nucleii are located deep within the white matter. Temporal lobe Occipital lobe Receives “somesthetic” sensations and proprioreception Parietal lobe Temporal lobe Occipital lobe Parietal lobe Frontal lobe Voluntary motor activity, speech, thought Temporal lobe Occipital lobe Primary motor cortex Somatosensory cortex Frontal lobe Parietal lobe Central sulcus Figure 5.11 (2) Page 149 Sensory homunculus Left hemisphere Temporal lobe Motor homunculus If you lose one sense, do others compensate? Auditory ability is enhanced with loss of vision even for just a few hours Mapping can be altered through experience – “plasticity” Posterior parietal cortex – transforms visual information into movement commands Premotor cortex Prefrontal cortex Posterior parietal cortex Parietal lobe Frontal lobe Temporal lobe Occipital lobe Cerebellum Associative areas: Prefrontal (association) cortex - plans voluntary activity, decision-making, creativity, and personality traits. Then the pre-motor cortex (w/ neighboring area) will orient the body, help plan and coordinate movements Muscle movement Pre Areas that communicate to the 1o motor cortex to control voluntary movement Premotor cortex Prefrontal cortex Posterior parietal cortex Language areas Broca’s area is responsible for speaking ability. Wernicke’s area functions for language comprehension. Lateralization of hemispheres corpus callosum Diencephalon Hypothalamus – Controls much of the endocrine system via pituitary gland Thalamus - performs some sensory processing, transmits signals to ‘higher’ areas Pineal – linked with circadian clock Diencephalon Thalamus Table 5.3 (1) Page 144 Midbrain Pons Midbrain Brain stem Pons Medulla Cerebellum Medulla Cerebellum Brain stem Brain stem and cerebellum Brain stem - Controls basic functions: breathing, heart rate, digestion, etc. Cerebellum maintains balance, enhances muscle tone, and coordinates skilled muscle activity Coordination and smooth movements require additional input Cerebellum – compares motor cortex output with what is happening in body. Important for acquiring physical skills (procedural memory) Basal nuclei – inhibits unwanted movements. Associated with Parkinson’s disease, Huntington’s disease Basal nuclei inhibits muscle tone selects and maintains purposeful muscle activity while inhibiting useless movement monitors and controls slow, sustained contractions (posture) Reticular activating system Visual impulses Reticular formation Brain stem Auditory impulses Spinal cord Sleep questions Why do we sleep? How does our physiology change with sleep? Interested in delta and theta brain waves in sleep Why can some people fxn on fewer hours of sleep and others require more? Sleep physiology and function Sleep is complex and electrically active Deep NREM sleep: body repair, build bone, muscle Rodents deprived of sleep live 3 weeks instead of normal 2-3 years BP, body temp, urine filtering, GI motility decrease. GH increases (cell repair, growth). Activity, breathing dependent on sleep stage. During REM body movement is inhibited except for face, eyes Sleep stages Stages defined by frequency and amplitude of EEG waves Theta Delta Theta How long should sleep last? Humans generally require 7-8 hours of sleep 10% require more 5% require less (some have mutation on DEC2 or BHLHE41 genes). They have reduced sleep but no less NREM sleep