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Homeostatic system and Drugs 藥理學科E501 詹銘煥 You have to think… How do drugs work in your body? Why is your body susceptible to the influence of drugs and other substances? Why do human beings like to abuse drugs? Key Terms Homeostasis: maintenance of internal stability or equilibrium Neurotransmitters: chemical messengers released by neurons Hormones: chemical messengers released into the blood by glands Endocrine system: relating to hormones, their functions, and sources Neurons: specialized nerve cells that make up the nervous system and release transmitters Learning Objectives The role of receptors in mediating the effects of drugs, hormones, and neurotransmitters. Distinguish between receptor agonists and antagonists. Neurotransmitters associated with drug addition. Identify which brain areas are most likely to be affected by drugs of abuse. How and why anabolic steroids are abused and the health impact attributed to abuse? Nerve cells (neurons) They can conduct bioelectric signals for long distances without any loss of signal strength. They possess specific intercellular connections with other nerve cells and with innervated tissues such as muscles and glands. Neurons can send discrete excitatory or inhibitory messages to their target cells. How do neurons communicate ? Neurotransmitters Receptors Electric transmission Chemical transmission Common neurotransmitters Acetylcholine: mild euphoria Norepinephrine: excitation Epinephrine: excitation Dopamine: euphoria Serotonin (5HT): aggressiveness GABA (gamma-aminobutyric acid): sedation Endorphins: mild euphoria, blockade of pain Plasma membrane The membranes of cells (3-6 nm) are effectively impermeable to ions and polar molecules. Receptors Receptors: proteins inserted in the plasma membranes of cells. They permit external chemical signaling molecules, the first messengers, to direct the activities of cells in a variety of ways with high specificity and precise control in terms of extent and duration. Key Terms Opiate receptors: receptors activated by opioid Endorphins: neurotransmitters that have narcoticlike effects Agonist: a type of substance that activates a receptor Antagonists: a type of substance that blocks a receptor Neurons: specialized nerve cells that make up the nervous system and release transmitters Neurotransmitters in brain-Drugs of abuse Acetylcholine: tobacco, nicotine Dopamine: amphetamines, cocaine Endorphins: narcotics GABA: alcohol, diazepam, barbiturates Serotonin: LSD (lysergic acid diethylamide) The PRP includes the dopaminergic pathway from the ventral tegmental area (VTA) to the nucleus accumbens (NA) and extending to the prefrontal cortex. Dopaminergic pathways are activated by the neurotransmitter, dopamine. The serotonin pathways in the brain Distribution of acetylcholine receptors in the brain Stress and anxiety affect nicotine tolerance and dependence. The stress hormone corticosterone reduces the effects of nicotine; therefore, more nicotine must be consumed to achieve the same effect. This increases tolerance to nicotine and leads to increased dependence. Studies in animals have also shown that stress can directly cause relapse to nicotine self-administration after a period of abstinence. In 1992, WHO for the first time, included tobacco smoke in the chapter dedicated to "MENTAL and BEHAVIOURAL DISORDERS caused by psychoactive substances." Nicotine, which is responsible for nicotine addiction, may be defined as a psycoactive substance whose action consists mainly in the activation of cerebral centers: 1) The dopaminergic mesolimbic system is regarded as the cerebral centre of pleasure and gratification, since the subject tries to recover the exhilarative effect of the product (CRAVING). The central nervous system Reticular activating system Basal ganglia Limbic system Cerebral cortex Hypothalamus The RAS is the attention center in the brain. It is the key to "turning on your brain," and seems to be the center of motivation. The RAS is connected at its base to the spinal cord where it receives information projected directly from the ascending sensory tracts. The brain stem reticular formation runs all the way up to the mid brain. As a result, the Reticular Activating System is a very complex collection of neurons which serve as a point of convergence for signals from the external world and from interior environment. RAS is very susceptible to the effects of drugs: LSD, cocaine, amphetamine, alcohol, barbiturates BG are the primary centers for involuntary and finely tuned motor functions, posture and muscle tone. Damage to BG may cause Parkinson’s disease. Heavy use of tranquilizers for psychotic patients can produce Parkinson-like syndromes. Limbic system It appears to contribute to the characteristics of the individual and the continuation of human life. The limbic system is responsible for feeding behavior, “fight and flight reactions”, aggression, the formation of memories and the emotional life. The limbic system receives input from many parts of the cerebral cortex and contains association areas where various aspects of sensory experience come together to form a single experience. Self-administration of stimulant drugs (amphetamine & cocaine) occurs in Limbic system. Limbic system’s transmitters: dopamine, NE, & 5-HT. The endocrine system The endocrine system consists of glands which release hormone into the bloodstream. Regulation of metabolism, growth, tissue repair, sexual behavior, etc. Hormone has a slower onset, a longer duration of action, and a more generalized target. The abuse of hormones Androgens: testosterone (natural androgen) Anabolic steroids: They are abused by many athletes & trainers Side effects: early heart disease, sudden death, the increase of LDL, lower HDL, an increase in tendon injuries, liver tumors, testicular atrophy, gynecomastia, male pattern baldness, severe acne, premature closure of growth plates in adolescents, emotional disturbances and other significant health risks. Designer steroids: tetrahydrogestrinone (2003), gastrinone, trenbolone ANABOLIC STEROIDS: THE ROAD TO THE GOLD OR THE ROAD TO THE GRAVE