Optimisation of cognitive performance in rodent operant (touchscreen) testing: Evaluation and effects of reinforcer strength.

Operant testing is a widely used and highly effective method of studying cognition in rodents. Performance on such tasks is sensitive to reinforcer strength. It is therefore advantageous to select effective reinforcers to minimize training times and maximize experimental throughput. To quantitatively investigate the control of behavior by different reinforcers, performance of mice was tested with either strawberry milkshake or a known powerful reinforcer, super saccharin (1.5% or 2% (w/v) saccharin/1.5% (w/v) glucose/water mixture). Mice were tested on fixed (FR)- and progressive-ratio (PR) schedules in the touchscreen-operant testing system. Under an FR schedule, both the rate of responding and number of trials completed were higher in animals responding for strawberry milkshake versus super saccharin. Under a PR schedule, mice were willing to emit similar numbers of responses for strawberry milkshake and super saccharin; however, analysis of the rate of responding revealed a significantly higher rate of responding by animals reinforced with milkshake versus super saccharin. To determine the impact of reinforcer strength on cognitive performance, strawberry milkshake and super saccharin-reinforced animals were compared on a touchscreen visual discrimination task. Animals reinforced by strawberry milkshake were significantly faster to acquire the discrimination than animals reinforced by super saccharin. Taken together, these results suggest that strawberry milkshake is superior to super saccharin for operant behavioral testing and further confirms that the application of response rate analysis to multiple ratio tasks is a highly sensitive method for the detection of behavioral differences relevant to learning and motivation.

Saccharin fading is not required for the acquisition of alcohol self-administration, and can alter the dynamics of cue-alcohol memory reconsolidation.

RATIONALE: Animal models of alcohol-seeking are useful for understanding alcohol addiction and for treatment development, but throughput in these models is limited by the extensive pretraining required to overcome the aversive taste of ethanol. Work by Augier et al. (Psychopharmacology 231: 4561-4568, 2014) indicates that Wistar rats will self-administer alcohol without water deprivation, exposure to sweetened ethanol solutions or intermittent access to ethanol. OBJECTIVES AND METHODS: We sought to replicate and extend the work of Augier et al. by comparing the acquisition of instrumental self-administration of ethanol in Lister-Hooded rats that had been previously saccharin faded (SF group) or not (NSF group). We also aimed to determine whether NMDA receptor antagonism with MK-801, given at memory reactivation, reduced subsequent ethanol-seeking behaviour in both groups of animals. Finally, we assessed the ethanol preference of SF and NSF rats using the two-bottle choice procedure. RESULTS: Both SF and NSF groups acquired instrumental self-administration of ethanol, though SF rats consumed fewer of the earned reinforcers. MK-801, given at memory reactivation, had different effects on NSF and SF rats: impairing the capacity of an ethanol-paired conditioned stimulus (CS) to support reinstatement in NSF rats, and enhancing it in SF rats. Finally, neither SF nor NSF rats showed a preference for ethanol. CONCLUSIONS: Our data support those of Augier et al. (Psychopharmacology 231: 4561-4568, 2014) that pretraining is unnecessary for rats to acquire instrumental self-administration of ethanol. Indeed, saccharin fading may produce a weaker memory that extinguishes more readily, thus accounting for the different effects of MK-801 on SF and NSF rats.