and Schwarcz, R., Lesions of striatal neurones with kainic acid provides a model for Huntington’s chorea... T., Rotational behavior in rats with unilateral striatal kainic acid lesions:
Trang 1An Operant Analysis of Fronto-Striatal Function in the Rat 223
observational recording of behaviour, and also allows for a greater efficiency incollecting and processing data
In addition to allowing detailed functional studies, operant tests also allow afunctional assessment of a wide variety of those surgical, cellular, or pharmacologicalinterventions with potential clinical relevance While hand testing and observationaltechniques may be more appropriate if the evaluation of a novel therapy is at anearly stage, operant tasks allow for a fuller evaluation of the functional efficacy oftreatments Moreover, an understanding of how particular neural structures mediatefunction is crucial to the design of such interventions.111
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in rats Behav Neurosci., in press, 1999.
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Trang 8for Studying Effects upon Acquisition and Consolidation
of Information
Sheldon B Sparber
Contents
I Introduction and Overview
A Choice of Autoshaping as a Behavioral Assay
B Wrongful Expectations of Simple, Linear Dose-Response Relationships
C Vasopressin and Enhanced Cognition or Arousal?
D Trimethyltin Neurobehavioral Toxicity and the Learning-Performance Distinction
E Effects of Pharmacological Manipulations Upon Performance:
Trang 9Use of Autoshaping with Non-Delayed and Delayed Reinforcement 233
autoshaped behavior is primarily a classically conditioned behavior, an tally conditioned behavior, a bridge between the two (S-R vs R-S contingencies)
instrumen-or a new class of behaviinstrumen-or with components of each, can be gleaned from the manychapters in the book edited by Locurto, Terrace and Gibbon3 entitled Autoshaping and Conditioning Theory
Although the majority of studies dealing with the phenomenon of autoshapinghave used a procedure whereby delivery of reinforcers was not contingent upon aspecified response, my own laboratory has taken advantage of the automaticity andlack of experimenter-induced bias conveyed by autoshaping and we too have utilized
a response-contingent component whereby the subject (normally a rat but we, asothers4 have, used autoshaping with chickens as well) is given the opportunity tomanipulate its environment (e.g., touching the extended lever, initiating its retractionearlier than programmed to do so noncontingently) leading to the delivery of areinforcing stimulus (e.g., food) slightly sooner than its delivery in the absence of
an operant (lever touch) response For protocols we generally use, the subject cannotearn more reinforcers during a daily session in which 12 to 30 or more trials arepresented and their session lengths cannot be shortened by more than a fraction,thereby most likely obviating a shortened session length as a reinforcing outcome(i.e., trials without an autoshaped response typically are comprised of the presenta-tion of a retractable lever for 15 s, followed by retraction and either immediatedelivery of a reinforcing stimulus or delaying the reinforcer for up to 8 or 9 s)followed by a random or fixed time ITI, typically averaging 45 s By introducing adelay of reinforcement we believe we have introduced a so-called working memorycomponent as a variation of the task and this has enabled us to demonstrate selectiveand specific effects of neurotoxic insults to the hippocampus and associated struc-tures (vide infra)
As is often the case, behavioral toxicologists, behavioral pharmacologists andpsychopharmacologists borrow procedures and protocols from the experimental andcognitive psychologists and because of their training and reliance upon conceptslike dose-response relationships, often discover a need to systematically manipulateantecedent and consequential variables which had not previously been carried outadequately by others Likewise, it may be necessary to modify the typical physicalenvironment used by others so that drug-behavior studies can be carried out in such
a manner that ancillary measures of unconditioned behaviors can also be recordedconcurrently, either automatically or via closed circuit television monitors and videorecorders for later off-line analyses
Because this contribution is for a book recommending and describing methods,
I have chosen to discuss the advantages and disadvantages of the variations ofautoshaping procedures we have used over the past 25 years I have also includedcomments on theoretical and philosophical issues, where apparently appropriate,and discussions or comments about the technology used and choice of data collec-tion, reduction, and statistical analyses
The last points are not especially restricted to autoshaping as a behavioralparadigm, or to behavioral neuroscience in particular, but are important enough for
a few comments at the outset because it has been my experience, in common withsome colleagues, that as technological advances have enabled us to collect more
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and more data, at faster rates, not enough attention has been paid to the importance
of experimental design, how the voluminous data will be handled once they arecollected and the validity or appropriateness of whichever statistical analytical pro-cedures are used In my laboratory this is a continuing, evolutionary process and wecontinue attempting to devise/design experiments which enable us to rely upon pre-planned statistical contrasts To the credit of most psychologists and behavioralneuroscientists, at least reasonable attempts at dealing with these issues are morecommonplace than has been my experience when attempting to interact or collab-orate with colleagues of a more reductionist persuasion I have, on more than a fewoccasions, asked a colleague who points to the obviously more intense band or spot
on a gel or chromatogram, derived from a single experiment (single subject’s orpooled tissue) that it is also obvious (at least living in the midwestern plains of theU.S.) that the world is flat All one has to do is to look out of the window to confirm
it Of equally great concern (frustration?) is trying to convince a colleague that 5 to
10 experiment(s) carried out with xenopus oocytes expressing one or another tor, but upon oocytes derived from a single female frog, is nothing more than oneexperiment with 5 to 10 replications and that standard parametric or nonparametricstatistical analytical procedures designed for independent observations from indi-viduals (or parts thereof), randomly assigned to one or another treatment condition,are not appropriate, even if he/she is willing to consider using such statisticalcontrasts
recep-Over the years we have used variations of autoshaped behavior acquisitionand/or maintenance to study the actions of drugs or toxins upon this class ofbehavior(s) in mature experimental subjects, either exposed to a drug or toxininsult during development (e.g., in ovo [chick] or in utero [rat] ) or after exposure
to drugs, withdrawal from them or exposure to toxins postnatally, at a more matureage Other laboratories have followed our lead and have used identical or similarprotocols to study the autoshaped acquisition of intravenous cocaine self-admin-istration,5 to study the effects of experimenter-administered cocaine uponautoshaped behavior acquisition,6 and to study effects of pyrogens/cytokines,which reportedly specifically disrupt or interfere with acquisition of food-rein-forced autoshaped behavior based upon the fact that the same behavior, onceestablished, was not affected by the same treatment.7
It has been the policy of my laboratory to attempt to give something back tothe discipline from which we have borrowed theoretical and/or methodologicalunderpinnings I believe our contributions in this regard can be gleaned to someextent from the publication list appended to this chapter Thus, I have chosen toemphasize some of the ways we have devised to maximize the use of autoshapedbehavior in order to control for as many potential confounding variables whichcan interfere with design, implementation, and, most importantly, the interpretation
of data derived from such studies Almost of necessity, it is a quasi-chronology
of the evolution of protocols currently in use in my laboratory (and those ofcolleagues who have asked for advice or patterned their work from one or more
of our publications in which autoshaped behavior was one of the protocols weutilized)
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the Chisso Chemical Company (responsible for dumping tailings into Minamata Bayand its surrounds) and the Japanese government accepted and confirmed the cause
of this strange malady decades afterward, controversy existed (and still exists) overthe likelihood that more subtle (CNS) dysfunction was much more widespread andinsidious than acknowledged Thus, in the late 1960s and early 1970s we initiatedstudies upon the developmental effects of exposure to CH3Hg during embryogenesis
of chickens,16 mice,17 and rats.18
There were three main reasons for using autoshaping as a behavioral assay forpurposes of studying autoshaped behavior in exposed rats Firstly, we wanted todetermine if we could demonstrate subtle cognitive or other dysfunctional behavioraleffects of prenatal exposure to otherwise apparently nontoxic doses of CH3Hgwithout the potential for introducing an experimenter bias by hand-shaping operantbehavior during the learning phase Secondly, we were interested in determining ifthere were critical or sensitive periods during development when such exposurecaused behavioral dysfunctional effects Lastly, we wanted to determine if autoshap-ing acquisition or performance, alone or upon a psychopharmacological challenge,could have predicted a human functional teratogenic effect of in utero exposure to
CH3Hg.18
At this juncture I’d like to discuss some of the advantages and disadvantages
of the choice of “technology,” experimental design, and the use of a pharmacologicalprobe for studying mature offspring exposed to doses of CH3Hg, given to theirpregnant mothers at different stages of pregnancy, which resulted in fetal exposure
to the same concentrations of CH3Hg during the perinatal period Only those (maleand female) offspring whose mothers were given a single dose of CH3Hg (by oralgavage) on the first day of gestation or on the seventh day proved to have beenaffected in some way While they autoshaped at rates comparable to control offspring,they were significantly less sensitive to the disrupting action of d-amphetamine uponestablished performance of food-reinforced autoshaped behaviors, compared withcontrols In these early experiments the food pellet reinforcers were delivered imme-diately upon retraction of the lever, whether or not the rat touched the extendedlever Offspring whose mothers were dosed on the 14th day of gestation and whoseperinatal body and/or brain concentrations of CH3Hg were not different from off-spring of the other treatment groups, were not noticeably different from controls,including their sensitivity to the autoshaped behavioral-disrupting action of d-amphetamine Therefore, we concluded that doses of CH3Hg that had absolutely noeffect upon standard parameters used in such studies (e.g., body weight gain bydams, litter size, litter weight, sex ratios, etc.) but which led to equivalent perinatalconcentrations of CH3Hg in offspring caused effects only in mature offspring whosemothers were dosed on the first or seventh, but not on the 14th day of gestation.These results indicated that a critical or sensitive period existed, manifested asreduced sensitivity to the disrupting action of d-amphetamine upon performance ofalready acquired autoshaped behavior The outcome of the experiment with d-amphetamine also confirmed our hypothesis that such pharmacological probes mightunmask a silent functional teratogenic effect and at the same time point to possibleneurochemical sources of the lesion The use of a range of doses of d-amphetamineenabled us to observe prenatal effects in both sexes, since it turned out that males
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