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Disruption of the US pre-exposure effect and latent inhibition in two-way active avoidance by systemic amphetamine in C57BL/6 mice

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Abstract

Rationale

Pre-exposure to either one of the two to-be-associated stimuli alone is known to reduce the efficiency of the learning of their association when they are subsequently paired explicitly. In classical conditioning, pre-exposure to the conditioned stimulus (CS) gives rise to latent inhibition (LI); and pre-exposure to the unconditioned stimulus (US) results in the US pre-exposure effect (USPEE). Considerable evidence supports an important role of central dopamine in the regulation and modulation of LI; it has been suggested that the USPEE may be similarly controlled by dopamine, but this parallelism has only been directly demonstrated in the conditioned taste aversion paradigm.

Objective

The present study tested this hypothesis by comparing the efficacy of systemic amphetamine treatment to affect the expression of LI and the USPEE in a two-way active avoidance paradigm.

Methods

C57BL/6 male mice were tested in active avoidance using a tone CS and a foot-shock US. Twenty-four hours before, they were pre-exposed to 100 presentations of the CS or the US, or to the test apparatus only. Amphetamine (2.5 mg/kg) or saline was administered before stimulus pre-exposure and conditioned avoidance test, in which the mice learned to avoid the shock by shuttling in response to the tone.

Results

Amphetamine disrupted both stimulus pre-exposure effects, thus, lending further support to the hypothesis that the USPEE is similar to LI in its sensitivity to dopamine receptor agonist. Hence, the USPEE paradigm may represent a valuable addition to the study of dopamine-sensitive processes of selective learning currently implicated in LI and Kamin blocking.

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Acknowledgment

The present study was supported by the Swiss Federal Institute of Technology and the National Centre for Competence in Research: Neural Plasticity and Repair, funded by the Swiss National Science Foundation. We thank Peter Schmid for his technical assistance, Jeanne Michel and Pascal Guela for their services in animal husbandry, and Dr. Frank Bootz for his veterinary expertise.

All experiments reported in this paper comply fully with the current laws of Switzerland where they were performed.

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Correspondence to Benjamin K. Yee.

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Tilly Chang and Urs Meyer contributed equally to the present paper.

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Chang, T., Meyer, U., Feldon, J. et al. Disruption of the US pre-exposure effect and latent inhibition in two-way active avoidance by systemic amphetamine in C57BL/6 mice. Psychopharmacology 191, 211–221 (2007). https://doi.org/10.1007/s00213-006-0649-z

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