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181lec4 - Psych 181 Dr Anagnostaras Lecture 4 Behavioral...

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Unformatted text preview: Psych 181: Dr. Anagnostaras Lecture 4: Behavioral Pharmacology Lecture Behavioral Behavioral Pharmacology Behavioral Pharmacology The study of the relationship between The the physiological actions of drugs and their effects on behavior and psychological function psychological q q Drugs do not create behaviors outside the Drugs normal species-typical repertoire normal They alter the probability of occurrence of They behaviors behaviors Set and setting The behavioral effects of drugs are due to The complex interactions amongst the pharmacological actions of drugs, the state of the organism (“set”), and the (“set”) and environmental circumstances surrounding drug administration (“setting”) (“setting”) Evaluating the behavioral effects of drugs Primary Evaluation Unconditioned effects on behavior q q q Motor activity q locomotion, catalepsy, balance, strength Seizures Eating and drinking Secondary evaluation Tests of more specific functions (either unconditioned or conditioned (learned) q Analgesia Tail-flick test Light source Hot plate test Secondary evaluation q Learning and memory -several different forms Spatial Radial Maze Task “Win-Shift” Lots of spatial (room) cues Rats/mice use these cues to avoid revisiting arms (ecologically valid) All arms baited, must not revisit arms •Different brain systems than non-spatial •Use spatial cues in room (posters, etc) to locate submerged platform (same place ea. time) •Measure latency to mount plaform & swim path (distance traveled to platform) •Different brain systems than visible platform Fear and Anxiety Secondary Eval • Anxiety • Elevated Plus Maze end for Exam1 Self-administration (Lecture 4 continued) q Schedules of reinforcement Positive reinforcement Presentation increases the probability of the Presentation increases preceding behavior preceding Negative reinforcement Removal increases the probability of the Removal increases preceding behavior preceding Punishment Decreases the probability of a behavior Ratio schedules Ratio Reinforcement is based in the number of Reinforcement responses made responses q Fixed vs. variable (FR vs. VR) Continuous reinforcement (FR1) Interval schedules Interval Reinforcement is based on the amount of time that Reinforcement has elapsed since the last reinforcement has Fixed vs. variable (FI vs. VI) q DRL schedules DRL (differential reinforcement of low rates) (differential Version of a FI; get reinforcement after fixed Version time, but if respond before time is up causes “time out” and resets clock “time Schedules of reinforcement Operant procedures used for two primary Operant reasons: reasons: 1) To ask questions about the stimulus 1) properties of drugs (“what does it feel like”) like”) 2) To ask questions about the reinforcing 2) and/or incentive properties of drugs (“will you work for it”) (“will Drugs as discriminative stimuli SD = stimulus that signals availability of reinforcement (e.g., red vs. green light) reinforcement Animals learn to respond when appropriate SD is present present Drugs can serve as a SD q Animals Animals learn to respond appropriately in presence of drug SD presence q SD is related to interoceptive cues of drug is Drugs as discriminative stimuli Method to ask animals about the interoceptive cues Method associated with different drugs associated Press left lever if on morphine > get food Press Right lever if given saline > get food Right Give new drug - is it like morphine? q Left lever - Yes q Right lever - No Drugs as discriminative stimuli Using drug discrimination techniques find Using that animals classify drugs just like humans that E.g., amphetamine and cocaine alike, but E.g., different than morphine, but morphine like heroin and other opiates heroin Measurement of drug reward Goal is to determine abuse potential of Goal different drugs and to study mechanisms by which drugs produce rewarding effects and dependence dependence q q q Measure effects on withdrawal symptoms Self-administration paradigms Conditional place preference Effects on withdrawal Steps: q q q Produce physical dependence with prototypical Produce drug (e.g., morphine) drug Withdraw and give unknown If block withdrawal symptoms will probably If produce similar dependence syndrome produce (Not conclusive) Self-administration paradigms Self-administration paradigms Procedures: q Substitution procedures q Choice procedures Predictive validity: All drugs self-administered by Predictive animals are also self-administered by people Self-administration paradigms Drugs that maintain self-administration amphetamines, barbiturates, cathinone, cocaine, amphetamines, codeine, ethanol, fentanyl, heroin, methadone, methamphetamine, MDMA, methylphenidate, morphine, nicotine, PCP, THC morphine, Drugs that do not aspirin, haloperidol, imipramine, lidocaine, aspirin, mescaline, LSD mescaline, Self-administration paradigms FR Schedules q Sizemore et al. (1997) typical measure rate or number of responses (or infusions) infusions) q inverted U curve Dose of Cocaine Self-administration paradigms FR Schedules Descending limb? q incapacity q satiety q loss of reward A n ce s n di g lim b De s ce n din gl im b Dose of Cocaine Self-administration paradigms FR Schedules De e sc di n ng b m li sc en din gl Descending limb? A q incapacity incapacity q satiety q loss of reward im b Sizemore et al. (1997) Dose of Cocaine Self-administration paradigms FR Schedules On ascending limb typically assume: q increase in rate = increase in reward in rate = increase in reward On descending limb, typically assume: q decrease {increase in rate = decrease in reward (represents a compensatory response to loss of (represents reward)} reward)} Self-administration paradigms Increase in rate = decrease in reward Fits dopamine (DA) antagonist studies q DA antagonists increase rate (as does DA decreasing dose) decreasing Self-administration paradigms Problem E.g., 6-OHDA lesion (decreased rate (decreased interpreted as decreased reward) decreased Roberts et al. (1980) Self-administration paradigms Problem “How can both an increase and a decrease in rate of drug intake be used to draw the same conclusion? The dilemma is unmistakable: rate is an ambiguous measure of reinforcing efficacy” (Arnold & Roberts, 1997) Self-administration paradigms Problem of rate Problem is old issue is Electrical self-stimulation Faster rate with lower of two current intensities, but choose higher of two intensities (Hodos & Valenstein, 1962) Self-administration paradigms Progressive ratio Progressive schedules schedules Progressive increase Progressive in responses required in 1, 2, 4, 6, 9, 12, 15, 20, 25, 1, 32, 40, 50, 62, 77, 95, 118, 145, 178, 219, 268, 328, 402, 492, 603 ... 402, (j = 0.20) Self-administration paradigms Progressive ratio Progressive schedules schedules Measure of Measure motivation to take drug (how hard will will work for it), defined by “breakpoint” “breakpoint” Self-administration paradigms “Breakpoint” (highest ratio achieved) “Breakpoint” Self-administration paradigms amphetamine “Breakpoint” Comparing different drugs DA antagonists vs. 6-OHDA cocaine Self-administration paradigms Problems: One data point, cumulative Problems: dosing, etc. dosing, Conditioned place preference Pavlovian context conditioning procedure q Pair Pair drug administration with place in environment environment q Take advantage of a principle of reward q stimuli that are rewarding, “elicit approach stimuli responses and maintenance of contact with the stimulus” the q On test day: measure where spend time Conditioned place preference Conditioned place preference Advantages q Simple q Limited training required q Test in non-drug state Disadvantages q Not Not measure drug reward but rewarding properties of secondary reinforcer properties Sample question Which schedule of reinforcement is Which used to calculate “breakpoint”? used (a) (b) (c) (d) (e) FR10 VI15 DRL schedule Variable ratio Progressive ratio ...
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