Expression of the CS- and US-Pre-Exposure Effects in the Conditioned Taste Aversion Paradigm and Their Abolition Following Systemic Amphetamine Treatment in C57BL6/J Mice

Abstract

In classical conditioning, pre-exposures to either the to-be-conditioned stimulus (CS) or unconditioned stimulus (US) can retard subsequent conditioning between the CS and US. The present experiment evaluated the expression of these two pre-exposure effects in mice of the C57BL6/J strain, one of the most common background strains for genetically altered mice. We tested whether their expression would be disrupted by amphetamine treatment (2.5 mg/kg, i.p.) in a conditioned taste aversion paradigm with sucrose as the CS and lithium chloride-induced gastric malaise as the US. We found that one pre-exposure (PE) to either the CS or the US reduced aversion to sucrose solution in the controls following conditioning, but no such tendency was evident in the amphetamine-treated mice. The present study represents the first report of amphetamine-induced disruption of the CS-PE effect (ie latent inhibition) in mice, and the first attempt to compare it directly with the US-PE effect in any species. It extended previous reports in rats and humans, suggesting that the sensitivity of latent inhibition to amphetamine is largely comparable across species, thereby lending credence to the use of the latent inhibition effect as a behavioral assay for psychotic-like phenotype in transgenic mice. The parallel observation in the US-PE effect further indicates that its expression, at least in the present conditioned taste aversion paradigm, may also be under similar influence of the dopaminergic system.

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

“…A key objective in this study is to test whether the same amphetamine treatment regime would also lead to the attenuation or abolition of the USPEE-namely, the retardation in active avoidance performance seen in animals having been repeatedly pre-exposed to the shock US. A positive outcome in this direction would be in keeping with the finding reported by Meyer et al (2004) in the CTA paradigm. However, our previous experience (e.g.…”

“…Recently, we have shown that LI and the USPEE are similarly abolished by systemic amphetamine (2.5 mg/kg, i. p.) in mice using a conditioned taste aversion (CTA) paradigm in which the animals learned to associate a flavored liquid with gastric malaise (Meyer et al 2004). The present study is designed to test the generality of this parallelism by extension to another associative learning paradigm, namely active avoidance learning, in the same species.…”

“…This is warranted because amphetamine is known to reduce liquid consumption in the CTA paradigm in both rats and mice (e.g. Russig et al 2003;Meyer et al 2004). Hence, the possibility that the expression of LI and USPEE was weakened as a result of the reduced consumption of the flavored CS during pre-exposure and conditioning, respectively, cannot be entirely excluded (Russig et al 2003;Meyer et al 2004).…”

“…adopted from our previous study using the CTA paradigm (Meyer et al 2004). Amphetamine was administered before stimulus pre-exposure and conditioning, separated by 24 h. The behavioural parameters selected to produce the LI and the USPEE were selected on the basis of our previous demonstration that these effects could be disrupted by a prenatal manipulation designed to precipitate the emergence of psychotic-like behaviour, including enhanced sensitivity to systemic amphetamine challenge at 2.5 mg/kg in mice (see Meyer et al 2005Meyer et al , 2006a.…”

“…Russig et al 2003;Meyer et al 2004). Hence, the possibility that the expression of LI and USPEE was weakened as a result of the reduced consumption of the flavored CS during pre-exposure and conditioning, respectively, cannot be entirely excluded (Russig et al 2003;Meyer et al 2004). In contrast, the numbers of CS presentations in all phases of a conditioned avoidance experiment are strictly under the control of the experimenter.…”