Parametric Changes in Response Equilibrium During an Intra-cranial Self Stimulation (ICSS) Task: Can Reward Value be Assessed Independently of Absolute Threshold?

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Abstract

EASTERLING, K.W. AND S.G. HOLTZMAN. Parametric changes in response equilibrium during an intra-cranial self stimulation (ICSS) task: can reward value be assessed independently of absolute threshold? NEUROSCI BIOBEHAV REV 21(1) 55–65, 1997.—Traditional ICSS methodologies have attempted to evaluate changes in the rewarding value of brain stimulation by assessing the lowest value of the stimulation that will support responding. However, orderly changes in supra-threshold indicants of hedonic magnitude such as titration point have been shown. In the present experiments, rats were trained to respond on two ICSS autotitration schedules in which every response on one lever produced stimulation of the medial forebrain bundle, and every Xth response decreased either the stimulation current or the stimulation frequency. At any time, a response on a second “reset” lever restored the stimulation current or frequency available on the stimulation lever to its starting level and operationally defined changes in “reward value”. In order to study this titration point measure, two response requirements (responses/stepdown; step size) and two stimulation parameters (initial stimulation level; train duration) were systematically varied. Under both current and frequency titration schedules, data indicated that response rate and titration point remained stable over repeated trials and multiple testing days—parameters being constant. Across all conditions, compared to the frequency titration schedule, subjects responding under the current titration schedule showed significantly higher titration points and lower rates of responding. Indicating the independence of rate and titration point data, parametric manipulations did not affect titration point and rate data concurrently. Results support the conclusion that titration point is a relative measure of “reward value” that is generally independent of response rate, but that is affected by manipulations that alter the amount of stimulation available between “resets”. Additional work is needed in order to determine the relationship between the magnitude of stimulation needed to maintain minimal responding and that needed to maintain response equilibrium in an autotitration task. Copyright © 1996 Elsevier Science Ltd.

Section snippets

INTRODUCTION

AS REVIEWED by Liebman [13], there are two fundamental assumptions underlying traditional bar-pressing measures of lateral hypothalamic ICSS used by pharmacologists: (i) response rate is predictive of the reward value of the stimulation, therefore; (ii) drug effects on response rates represent changes in reward. However, it is generally acknowledged that these assumptions are true only for a lower or submaximal range of stimulation intensities. For example, only if the current intensity is kept

Subjects and Surgical Procedures

Subjects were six adult male Sprague-Dawley rats (Charles-River, Wilmington, MA). Prior to surgery, and during experiments, subjects were individually housed in standard polycarbonate cages with free access to food and water. The colony room was maintained under a 12:12 light-dark cycle with lights on at 06.00. Each weighed 250–350 g at the time of surgery.

Subjects were anesthetized with a mixture of pentobarbital and chloral hydrate (EquithesinTM; 3.3 ml/kg, IP) and placed in the stereotaxic

RESULTS

Fig. 1 depicts rate-per-step data for subjects (n=6) responding under both autotitration schedules in the third of five consecutive constant-parameter trials. These data indicate that, although they begin with identical stimulation parameters (first 15 responses, step 1) and comparable rates, subjects responding during 5% current stepdowns exhibit a significantly (F(6,30) = 3.96) sharper drop-off in rate at subsequent steps than they do when responding during 5% frequency stepdowns. The sharper

DISCUSSION

Each schedule generated mean titration point data resulting from approximately 15–20 determinations within a 15-min trial. During five consecutive constant-parameter trials, titration point, rate, and number-of-resets data remained stable as subjects responded over the course of a 2.5-h testing session. This occurred under both autotitration schedules evaluated. Therefore, both autotitration tasks may serve as stable baseline schedules against which drug or parametric manipulations may be

Acknowledgements

This investigation was supported by NIH Grants DA00541 and DA03413, and by Research Scientist Award K05/DA00008 to S.G.H. Special thanks to Dr Darryl B. Neill for helpful discussion of the data.

References (32)

  • G.J Schaefer et al.

    Free-operant and auto-titration brain self-stimulation procedures in the rat: A comparison of drug effects

    Pharmac. Biochem. Behav.

    (1979)
  • T.F Seeger et al.

    Pentobarbital induces a naloxone-reversible decrease in mesolimbic self-stimulation threshold

    Pharmac. Biochem. Behav.

    (1981)
  • L Yavich et al.

    A comparison of the effects of individual organic solvents and their mixture on brain stimulation reward

    Pharmac. Biochem. Behav.

    (1994)
  • P Zarevics et al.

    Simultaneous rate-independent and rate-dependent assessment of intracranial self-stimulation: Evidence for the direct involvement of dopamine in brain reinforcement mechanisms

    Brain Res.

    (1979)
  • E Coulombe et al.

    Fitting intracranial self-stimulation data with growth models

    Behav. Neurosci.

    (1987)
  • D.E Edmonds et al.

    Parametric analysis of brain stimulation reward in the rat. III. Effect of performance variables on the reward summation function

    J. Comp. Physiol. Psychol.

    (1974)
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