Psyc 362Class Notes for Exam 1--Chapter 4 continued, end of exam 1 material2/17/15Drug effectiveness● Dose-response (DR) curve: depicts relationshipbetween 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’tproduce a stronger effect● Therapeutic index: how close the poptimal effect of thedrug is to the amount we induce○ effectiveness of drug relative to its safety○ Dose of toxic effect in 50% of participants/Dose ofdesired effect in 50% of participantsRepeated administration of drug may alter effectivenessTolerance: overtime, same dosage has a diminishing effect. it takes a larger dosage to maintainconstant 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 ormarijuana)● Often related to changes in receptorsPlacebo 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 brainsynaptic transmission: transmitter substances are1. synthesized2. stored in vesicles3. released in postynaptic cleft4. binded to a receptor in the postsynaptic membrane5. 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 chennelsantagonist-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 facilitatoryNT binding to receptors produce either EPSPs or IPSPsGlutamate (most abundant NT in brain) produces EPSPsGABA (second most abundant) produces IPSPsNeuromodulators are chemicals altering action of systems of neurons that transmit information. using Glutamate or GABAEX: ACh-learing facilitationNorepinephrine (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 SceupolamineMonoamine NTs: Da, NE, EPI, and 5-HT1. 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 movementii. Mesolimbic pathway system projects ot limbic system (nucleus accombens, amygdala, hippocampus) from the ventral tegmental area to the cortexiii. Mesocortical system projects from the ventral temental area to the cortex; is involved in short-term memory, planning, strategyb. DA receptors are metabotropic: D1 is postsynaptic only, and D2 is pre and postsynapticc. drug DA interactionsi. AMPT blocks tyrosine enzyme that creates DA, preventing the conversionof tyrosine to L-Dopaii. Reserpine prevents storage of dopamine within vesiclesiii. Cocaine blocks reuptake of DA, increasing the presence of DA for a longer period of time in Postsynaptic cleftiv. 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 systemse. NE interacts with 4 receptor types in the braini. Alpha and Beta Adrenergic receptors both have two subtypes (a and be) and all are metabotropic.f. Most important