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Related Experiment Videos

State-dependent behavioural sensitization: evidence from a chlordiazepoxide state.

D N Stephens1, T D Elliman, S J Dunworth

  • 1Laboratory of Experimental Psychology, University of Sussex, Brighton, UK. dns@biols.susx.ac.uk

Behavioural Pharmacology
|July 6, 2000
PubMed
Summary

Behavioral sensitization to amphetamine requires a consistent internal state. If the internal state changes, such as with chlordiazepoxide, sensitization to amphetamine may be blocked.

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Area of Science:

  • Neuroscience
  • Psychopharmacology
  • Behavioral Science

Background:

  • Behavioral sensitization to psychomotor stimulants is a key phenomenon in neuroscience.
  • The state-dependency hypothesis suggests sensitization is expressed only when the internal state matches the sensitization development phase.
  • N-methyl-D-aspartate (NMDA) receptor antagonists have been observed to block sensitization, but the underlying mechanisms require further investigation.

Purpose of the Study:

  • To investigate the state-dependency hypothesis of behavioral sensitization.
  • To determine if chlordiazepoxide (CDP) can block amphetamine-induced behavioral sensitization.
  • To differentiate the effects of CDP from NMDA receptor antagonism in sensitization studies.

Main Methods:

  • Mice received daily injections of amphetamine + chlordiazepoxide (CDP), amphetamine + saline, CDP + saline, or saline + saline for 8 days.

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  • Animals were challenged with amphetamine + saline and CDP + saline on days 9 and 10 in a counterbalanced design.
  • Locomotor activity was measured to assess sensitization and state-dependency.

    • Main Results:

    • Both groups receiving amphetamine showed sensitization over the initial 8 days, indicated by increased locomotion.
    • Mice treated with amphetamine + CDP failed to exhibit a sensitized response when challenged with amphetamine alone.
    • The chlordiazepoxide (CDP) + saline group did not display locomotor sensitization, and CDP does not act on NMDA receptors.

    Conclusions:

    • The findings support the state-dependency hypothesis, indicating that a consistent internal state is crucial for expressing behavioral sensitization.
    • The study highlights the importance of considering drug-induced internal states as critical contextual factors in sensitization research.
    • Blockade of sensitization by CDP suggests that internal state, not solely NMDA receptor activity, influences the expression of sensitization to psychomotor stimulants.