Psyc 362 Class Notes for Exam 1 Chapter 4 continued end of exam 1 material 2 17 15 Drug effectiveness Dose response DR curve depicts relationship between drug dose and magnitude of drug effect shows that drugs can have more than one effect drugs vary in effectiveness based on different sites of action affinities for receptors after a certain point increase in dosage doesn t produce a stronger effect Therapeutic index how close the poptimal effect of the drug is to the amount we induce effectiveness of drug relative to its safety Dose of toxic effect in 50 of participants Dose of desired effect in 50 of participants Repeated administration of drug may alter effectiveness Tolerance overtime same dosage has a diminishing effect it takes a larger dosage to maintain constant effect Withdrawal effects are often the opposite of the drug the ddrug effect and often accompanied by tolerance Both can relect a decreased drug receptor binging or reduced postynaptic action of the drug Senitization repeated drug use results in heightened drug effectiveness sometimes cocaine or marijuana Often related to changes in receptors Placebo effect a control group must be used to be sure of any behavior effects of the drug they observe are due to specific effects of drug Placebo is the inert substance given to an organism in lieu of a physiologically active drug it is used experimentally to control for the effects of drug administration belief that something is going to effect us will induce slight changes in the brain synaptic transmission transmitter substances are 1 synthesized 2 stored in vesicles 3 released in postynaptic cleft 4 binded to a receptor in the postsynaptic membrane 5 terminated by different means Drugs may work at many or just one of these processes Many drug effects mediated by interactions with the post synaptic membrane but receptors may have a variety of conformations have sites for various substances Agonist substance mimics facilitates or enhances the effect of the endocgenous chemical those produced by the brain direct agonist drug binds and activates a receptor indirect agonist attaches to alternative sites in the receptors and facilitates the opening of ion chennels antagonist substance impeding or reducing effect Can be a receptor blocker in which it binds to but doesn t activate receptors and prevents endogenous substance from binding indirect antagonist drugs attach to a binding site and interfere with normal action of receptor Sites of Drug actions effects on storage and release of NT transporters are important capable of reuptaking NTs into the presynaptic terminal buttons effects on receptors noncompetative binding effect process but doesnt displace endogenous chemical doesn t interfere with binding site for principal ligand two processes accomplished to terminate PSP reuptake or destruction of NT Presynaptic autoreceptors regulate amount of NT released from the axon terminal drugs can activate or reduce the amount of NTs released Presynaptic heteroreceptors sensitive to NT released by another neuron can be inhibitory or facilitatory NT binding to receptors produce either EPSPs or IPSPs Glutamate most abundant NT in brain produces EPSPs GABA second most abundant produces IPSPs Neuromodulators are chemicals altering action of systems of neurons that transmit information using Glutamate or GABA EX ACh learing facilitation Norepinephrine NE Increase readiness to act alterness Dopamine DA activation of voluntary movements ACh is the primary NT secreted by efferent CNS cells and it helps activate muscles implicated in regulation of learning memory control of movement and mood ACh neurons related to arousal places basal forebrain and brainstem region in the brain are found in dorsal lateral pons elicitates REM sleep arousal medial septum controls hippocampus basal forebrain learning especially perception activation of corteces ACh released in the brain results in facilitating effects in the PNS ACh neurons are found in autonomic ganglia engagement and neuromuscular junctions activation of muscle movement Synthesis requires 2 elements Choline and Acetyl CoA is dependent on Choline 2 combined in an enzyme which then produce ACh COA arises from metabolism drugs effecting ACh hemicholsium inhibits the reuptake of Choline ACh release requires calsium ion entry release can be blocked by botulinum toxin while black widow spider venom can promote release ACh is degraded by AChE enzyme ACh receptors ACh acts through Nicotinic and muscarinic receptors Nicotonic ionotropic receptors in skeletal muscle adrenal medulla neuromuscular junction and in the brain agonist ACh Nicotine antagonist d tunocurarine and curare Muscarinic metabotropic receptors in heart and smooth muslce found in PNS and brain agonist ACh muscarine antagonist Atropine and Sceupolamine Monoamine NTs Da NE EPI and 5 HT 1 Catecholamines includes DA NE EPI adrenalin epinephrine NOTE synthesis of DA and NE DA is in synthetic pathway of NE some drugs that have enzyme to produce DA can sometimes produce NE not the other way around though a DA is used in several nerualsystems i Nigrostriatal system projects from substantia nigra to the caudate nucleus and putmen controls movement ii Mesolimbic pathway system projects ot limbic system nucleus accombens amygdala hippocampus from the ventral tegmental area to the cortex iii Mesocortical system projects from the ventral temental area to the cortex is involved in short term memory planning strategy b DA receptors are metabotropic D1 is postsynaptic only and D2 is pre and postsynaptic c drug DA interactions i AMPT blocks tyrosine enzyme that creates DA preventing the conversion of tyrosine to L Dopa ii Reserpine prevents storage of dopamine within vesicles iii Cocaine blocks reuptake of DA increasing the presence of DA for a longer period of time in Postsynaptic cleft iv MAO cause degrading of DA d NE noradrenaline is synthesized form DA within vesicles i NE nuerons located in numerous regions of Pons medulla and one in the thalamus that gives rise to NE fiber systems e NE interacts with 4 receptor types in the brain i Alpha and Beta Adrenergic receptors both have two subtypes a and be and all are metabotropic f Most important source is NE is the Locus Coeruleus contains a very large of NE cells that project to the rest of the brain which is important in arousal sleep and has a nucleus in the dorsal pons 2 Indolamines seratonin 5 HT a cells are mostly located in gut with only 2 in