Advertisement

Psychopharmacology

, Volume 174, Issue 3, pp 396–405 | Cite as

Free operant and discrete trial performance of mice in the nine-hole box apparatus: validation using amphetamine and scopolamine

  • Jean-Charles Bensadoun
  • Simon P. Brooks
  • Stephen B. DunnettEmail author
Original Investigation

Abstract

Rationale

To determine the suitability of the nine-hole box to characterise mouse performance on a free operant task and a discrete trials task, and to validate the tests by probing whether d-amphetamine and scopolamine modify performance of the task as predicted.

Objectives

To demonstrate the functionality and efficiency of the mouse nine-hole box for the evaluation of performance under fixed- (FR) and progressive-ratio (PR) operant schedules, as well as under a three-choice visual discrimination task and subsequent reversals of the task. In addition, sensitivity of the apparatus was assessed using pharmacological challenges.

Methods

C57BL/6J were tested on CRF, FR5, FR10, FR20, and a modified PR3 schedule. Behavioural response to d-amphetamine sulphate (0.1, 0.3, and 2.0 mg/kg for FR and 0.1, 0.3, and 1.0 mg/kg for PR) was assessed. In a separate group of mice trained on a three-choice visual discrimination task, the task was reversed (light+, dark+, light+, dark+) 3 times to determine acquisition and reversal of the visual discrimination rule. Scopolamine hydrobromide was examined in this paradigm with the reversal task, and was used to determine learning acquisition and rule reversal learning.

Results

Mice rapidly acquired the FR and PR schedules, as well as both three-choice visual discrimination procedures in the nine-hole box. d-Amphetamine significantly reduced performance on the FR5 and FR10 schedules as shown by the reduction in the number of rewarded responses and the increases in various latency measurements. As expected, d-amphetamine induced an increase in the break point and eliminated the pauses that occurred on high ratio schedules under the PR3 paradigm. Pretreatment of scopolamine decreased accuracy in the three-choice visual discrimination task.

Conclusions

The nine-hole box is an effective tool to assess operant behaviours in mice following pharmacological manipulation validating the utility of this apparatus for the behavioural evaluation of drug-induced and transgenic models of neurodegenerative disorders.

Keywords

Operant Mouse Fixed-ratio Progressive-ratio Drugs Visual discrimination 

Notes

Acknowledgement

Dr. J.C. Bensadoun was supported by the Swiss National Science Foundation. The work was funded by grants from the MRC and the BBSRC.

References

  1. Baron SP, Meltzer LT (2001) Mouse strains differ under simple schedule of operant learning. Behav Brain Res 118:143–152CrossRefPubMedGoogle Scholar
  2. Brasted PJ, Robbins TW, Dunnett SB (1999) Distinct roles for striatal subregions in mending response processing revealed by focal excitotoxic lesions. Behav Neurosci 113:253–264CrossRefPubMedGoogle Scholar
  3. Cheal M (1981) Scopolamine disrupts maintenance of attention rather than memory processes. Behav Neurol Biol 33:163–187Google Scholar
  4. Christakou A, Robbins TW, Everitt BJ (2001) Functional disconnection of a prefrontal cortical-dorsal striatal system disrupts reaction time performance: implications for attentional function. Behav Neurosci 115:812–815PubMedGoogle Scholar
  5. Cousins MS, Wei W, Salamone JD (1994) Pharmacological characterization of performance on a concurrent lever pressing/feeding choice procedure: effects of dopamine antagonist, cholinomimetic, sedative and stimulant drugs. Psychopharmacology 116:529–537PubMedGoogle Scholar
  6. Depoorte R, Perrault G, Sanger DJ (1999) Intracranial self-stimulation under a progressive ratio schedule in rats: effects of strength of stimulation, d-amphetamine, 7-OH-DPAT and haloperidol. Psychopharmacology 142:221–229Google Scholar
  7. Durkin TP, Cazala P, Garcia R (2000) Trans-synaptic mechanisms controlling cholinergic neuronal activation in the septo-hippocampal and the nBM-cortical cholinergic pathways: differential roles in memory and attentional processes ? In: Numan R (ed) The behavioural neuroscience of the septal region. Springer, New York, pp 146–174Google Scholar
  8. Estape N, Steckler T (2002) Cholinergic blockade impairs performance inoperant DNMTP in two inbred strains of mice. Pharmacol Biochem Behav 72:319–334CrossRefPubMedGoogle Scholar
  9. Everitt BJ, Robbins TW (1997). Central cholinergic systems and cognition. Ann Rev Psychol 48:649–684Google Scholar
  10. Freund G, Walker DW (1972). Operant conditioning in mice. Life Sci 11:905–914CrossRefGoogle Scholar
  11. Gill TM, Sarter M, Givens B (2000) Sustained visual attention performance-associated prefrontal neuronal activity: evidence for cholinergic modulation. J Neurosci 20:4745–4757PubMedGoogle Scholar
  12. Glass MC, Billington CJ, Levine AS (1999) Opioids and food intake: Distributed functional neural pathways ? Neuropeptides 33:360–368CrossRefPubMedGoogle Scholar
  13. Glick SD, Muller RU (1971) Paradoxical effects of low doses of d-amphetamine in rats. Psychopharmacologia 22:396–402Google Scholar
  14. Golub MS, Germann SL (1998) Aluminum effects on operant performance and food motivation in mice. Neurotoxicol Teratol 20:421–427CrossRefPubMedGoogle Scholar
  15. Hayward MD, Low MJ (2001) The effect of naloxone on operant behaviour for food reinforcers in DBA/2 mice. Brain Res Bull 56:537–543CrossRefPubMedGoogle Scholar
  16. Heyser CJ, Fienberg, AA, Greengard P, Gold LH (2000) DARPP-32 knockout mice exhibit impaired reversal learning in a discriminated operant task. Brain Res 867:122–130CrossRefPubMedGoogle Scholar
  17. Higgs S, Deacon RMJ, Rawlins JNP (2000) Effects of scopolamine on a novel choice serial reaction time task. Eur J Neurosci 12:1781–1788CrossRefPubMedGoogle Scholar
  18. Humby T, Laird FM, Davies W, Wilkinson LS (1999) Visuospatial attentional functioning in mice: interactions between cholinergic manipulations and genotype. Eur J Neurosci 11:2813–2823PubMedGoogle Scholar
  19. Jones DNC, Higgins GA (1995) Effect of scopolamine on visual attention in rats Psychopharmacology 120:142–149Google Scholar
  20. Larson SJ, Romanoff RL, Dunn AJ, Glowa JR (2002) Effects of interleukin-1β on food maintained behaviour in the mouse. Brain Behav Immun 16:398–410CrossRefPubMedGoogle Scholar
  21. Levine AS, Morley JE, Gosmell BA, Billington CJ, Bartness TJ (1985) Opioids and consummatory behaviour. Brain Res Bull 14:663–672CrossRefPubMedGoogle Scholar
  22. Miczek KA, Haney M (1994) Psychomotor stimulant effects of d-amphetamine, MDMA and PCP: aggressive and schedule controlled behaviour in mice. Psychopharmacology 115:358–365PubMedGoogle Scholar
  23. Muir JL, Robbins TW, Everitt BJ (1994) AMPA-induced lesions of the basal forebrain: a significant role for the cortical cholinergic system in attentional function. J Neurosci 14:2313–2326PubMedGoogle Scholar
  24. Poling A, Cleary J, Jackson K, Wallace S (1981) d-Amphetamine and phencyclidine alone and in combination: effects on fixed ratio and interresponse-time-greater-than-t responding of rats. Pharmacol Biochem Behav 15:357–361CrossRefPubMedGoogle Scholar
  25. Poncelet M, Chermat R, Soubrie P, Simon P (1983) The progressive ratio schedule as a model for studying psychomotor stimulant activity of drugs in the rat. Psychopharmacology 80:184–189Google Scholar
  26. Robbins TW (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology 163:362–380CrossRefPubMedGoogle Scholar
  27. Rogers RD, Baunez C, Everitt BJ, Robbins TW (2001) Lesions of the medial and lateral striatum in the rat produce differential deficits in an attentional performance. Behav Neurosci 115:799–811PubMedGoogle Scholar
  28. Schaefer GJ, Michael RP (1988) An analysis of the effects of amphetamine on brain stimulation behaviour. Behav Brain Res 29:93–101PubMedGoogle Scholar
  29. Sparber SB, Fossum LH (1984) Amphetamine cumulation and tolerance development: concurrent and opposing phenomena. Pharmacol Biochem Behav 20:415–424CrossRefPubMedGoogle Scholar
  30. Steckler T, Sauvage M, Holsboer F (2000) Glucocorticoid receptor impairment enhances impulsive responding in transgenic mice performing on a simulataneous visual discrimination task. Eur J Neurosci 12:2559–2569CrossRefPubMedGoogle Scholar
  31. Sweirgiel AH, Smagin GN, Dunn AJ (1997) Influenza virus infection of mice induces anorexia: comparison with endotoxin and interleukin-1 and the effects of indomethacin. Pharmacol Biochem Behav 57:389–396CrossRefPubMedGoogle Scholar
  32. Van Gaalen MM, Stenzel-Poore M, Holsboer F, Steckler T (2003) Reduced attention in mice overproducing corticotropin-releasing hormine. Behav Brain Res 142:69–79CrossRefPubMedGoogle Scholar
  33. Wenger GR, Dews PB (1976) The effects of phencyclidine, ketamine, d-amphetamine and pentobarbital on schedule-controlled behaviour in the mouse. J Pharmacol Exp Ther 196:616–624PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Jean-Charles Bensadoun
    • 1
  • Simon P. Brooks
    • 1
  • Stephen B. Dunnett
    • 1
    Email author
  1. 1.Brain Repair Group, School of BiosciencesCardiff UniversityCardiffUK

Personalised recommendations