Haloperidol and clozapine antagonise amphetamine-induced disruption of latent inhibition of conditioned taste aversion

Holger Russig, Aneta Kovacevic, Carol A. Murphy, Joram Feldon

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: Latent inhibition (LI) describes a process by which repeated pre-exposure of a stimulus without any consequence retards the learning of subsequent conditioned associations with that stimulus. It is well established that LI is impaired in rats and in humans by injections of the indirect dopamine agonist amphetamine (AMPH), and that this disruption can be prevented by co-administration of either the typical neuroleptic haloperidol (HAL) or the atypical neuroleptic clozapine (CLZ). Objectives: Most of what is known of the pharmacology of LI is derived from studies using either the conditioned emotional response or the conditioned active avoidance paradigm. The goal of the present study was to determine whether these results would generalize to the conditioned taste aversion assay. Methods: We tested whether AMPH (0.5 mg/kg) pretreatment would disrupt LI of a conditioned aversion to sucrose, and if so, which stage of the procedure is critical for mediating the disruption; in addition, we tested whether HAL (0.2 mg/ kg) or CLZ (5.0 mg/kg) could restore such an expected LI disruption. Results: We determined that AMPH disrupted LI when it was injected before pre-exposure and prior to conditioning, but not if the rats were injected before either stage alone. When HAL or CLZ was given 40 min before AMPH (before both pre-exposure and conditioning), it blocked LI disruption. Conclusion: These results are in line with the pharmacology of LI as derived from other conditioning paradigms. We conclude that the pharmacological regulation of LI in the CTA paradigm is similar to what has been observed previously in the conditioned emotional response and the conditioned active avoidance paradigms.

Original languageEnglish
Pages (from-to)263-270
Number of pages8
JournalPsychopharmacology
Volume170
Issue number3
DOIs
StatePublished - Nov 2003
Externally publishedYes

Keywords

  • Amphetamine
  • Clozapine
  • Conditioned taste aversion
  • Haloperidol
  • Latent inhibition

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