Effects of multi-modal cues on conditioned place preference in C57BL/6J and DBA/2J mice

Abstract

Rationale Previous work has shown that some mouse strains (e.g., DBA/2J [D2]) readily develop robust ethanol-induced conditioned place preference (CPP) while others (e.g., C57BL/6J [B6]) do not. Though commonly interpreted as a difference between strains in sensitivity to ethanol reward, other explanations for this finding are possible. Objectives To explore the hypothesis that variation in sensitivity to contextual cues underlies CPP differences, the present work investigated ethanol-induced CPP in D2 and B6 mice trained with a standard tactile (floor) cue procedure compared to mice trained with tactile plus visual-spatial cues. Methods In an unbiased CPP procedure, mice were assigned to either a single element cue (one-compartment apparatus with tactile cue presented in the dark) or multimodal cues (two-compartment apparatus with distinct tactile floors and lights on). To track CPP development, mice received preference tests during training in addition to a final test. Results Adding visual-spatial cues accelerated CPP acquisition in both D2 and B6 mice. However, this enhancement was observed after just one ethanol-conditioning trial in D2 mice, but was observed only after four ethanol-conditioning trials in B6 mice. Differences between groups trained with single or multimodal cues disappeared as conditioning reached asymptote, with D2 mice showing a more rapid loss of the effect and a higher maximum CPP. Conclusions Although multimodal cues produce more rapid conditioning, their inability to reduce or eliminate strain differences in CPP supports the interpretation that these strains differ in their sensitivity to ethanol reward.

Amygdala circuit mechanisms underlying alcohol seeking

“…Neuronal activity of BLA Thy1+ neurons responding to repeated pairing of alcohol and context Since alcohol-mediated CPP depends on learning and memory processes associating alcohol exposure and context information, mice were subjected to a CPP procedure in which B6 mice consistently developed robust CPP responses (Figure 1a). As shown in previous literature 21, 22 , mice conditioned with alcohol (saline/EtOH or S/E) spent significantly longer time in a compartment associated with alcohol injection (Figure 1b, c), indicating that alcohol had induced a place preference via an association between the context and the rewarding effects of alcohol.…”

In search of a conditioned place preference test to assess the severity of experimental procedures

“…This was successfully done before in other studies [29, 47, 58]. Flooring materials combine multiple cues, including visual, tactile and olfactory cues multiple cues which can improve CPP acquisition [20]. Thus, mice should have been able to easily discriminate between the two chosen CS in this experiment – which can be confirmed as the mice showed a significant preference for one of the CS from the start.…”

“…When planning a CPP, the choice of the CS is important, meaning whether to use visual [6], tactile [16], olfactory cues [14], or a combination of those [3,19,20]. This choice should not be underestimated as some stimuli are easier associated with specific reinforcers (US) than other [21].…”

Inbred Mice Again at Stake: How the Cognitive Profile of the Wild-Type Mouse Background Discloses Pathogenic Effects of APP Mutations

“…Considering strain-specific levels of performance, it became rapidly evident that a majority of tasks in which C57 performed poorly were those in which DBA performed well, and vice versa. Beyond their aforementioned superiority in the Lashley maze and active avoidance, DBA mice were found to score better than C57 in cue-based fear conditioning (Paylor et al, 1994 ; Ammassari-Teule et al, 2000 ) and ethanol-induced conditioned place preference (Cunningham and Shields, 2018 ). On the one hand, these findings pointed out the remarkable ability of DBA to detect relevant elemental sensory stimuli to rapidly form stimulus–response associations in pavlovian or instrumental conditioning paradigms, or to implement egocentric orientation in spatial tasks.…”

“…However, a gradual increase in the stimulus duration was found to progressively abolish interstrain differences, thereby suggesting that C57 benefited for longer cue presentation to disentangle them from the context (Renzi and Sansone, 1971 ). Interestingly, Cunningham and Shields ( 2018 ) explored more recently the possibility that the most robust ethanol-induced conditioned place preference (CCP) shown by DBA compared to C57 might depend on strain differences in sensitivity to contextual cues. They found that compared to single cueing, multiple cueing increased CCP in both strains but that this effect disappeared more rapidly in DBA and was not sufficient to elevate the CCP performance of C57 to the level of DBA.…”