The use of ball pits and playpens in laboratory Lister Hooded male rats induces ultrasonic vocalisations indicating a more positive affective state and can reduce the welfare impacts of aversive procedures

The advancement and quality of science rely on research that is robust and unbiased in its experimental design, execution, analysis, and reproducibility. In preclinical research, a better understanding of animal emotions and refinement of their husbandry, housing, and handling are important goals in providing good animal welfare in a laboratory setting which underpins rigorous research quality. Induction of positive emotional state in animals is a key component of their well-being, and one approach is to increase their environmental complexity using, for example, ball pits or playpens in rats. In this study, we recorded 50 kHz ultrasonic vocalisations (USVs) during animals’ exposure to the ball pit and playpen. We have previously shown that 50 kHz USVs provide a graded and quantifiable measure of an animal’s emotional state, and here find that access to the ball pit and playpen increases 50 kHz USVs, indicative of a more positive affective state. Using our affective bias test (ABT) we next quantified the animals’ emotional response to an aversive intervention and whether this could be attenuated by access to a playpen. The playpen exposure completely mitigated the negative affective state induced by an anxiogenic drug when compared with animals who experienced the drug in the home cage. Together, these findings suggest ball pits and playpens provide a simple and effective method to improve the welfare of laboratory rats and reduce the cumulative suffering they experience from their housing conditions and minor, aversive procedures

Rapid-acting antidepressant drugs modulate affective bias in rats

How rapid-acting antidepressants (RAADs), such as ketamine, induce immediate and sustained improvements in mood in patients with major depressive disorder (MDD) is poorly understood. A core feature of MDD is the prevalence of cognitive processing biases associated with negative affective states, and the alleviation of negative affective biases may be an index of response to drug treatment. Here, we used an affective bias behavioral test in rats, based on an associative learning task, to investigate the effects of RAADs. To generate an affective bias, animals learned to associate two different digging substrates with a food reward in the presence or absence of an affective state manipulation. A choice between the two reward-associated digging substrates was used to quantify the affective bias generated. Acute treatment with the RAADs ketamine, scopolamine, or psilocybin selectively attenuated a negative affective bias in the affective bias test. Low, but not high, doses of ketamine and psilocybin reversed the valence of the negative affective bias 24 hours after RAAD treatment. Only treatment with psilocybin, but not ketamine or scopolamine, led to a positive affective bias that was dependent on new learning and memory formation. The relearning effects of ketamine were dependent on protein synthesis localized to the rat medial prefrontal cortex and could be modulated by cue reactivation, consistent with experience-dependent neural plasticity. These findings suggest a neuropsychological mechanism that may explain both the acute and sustained effects of RAADs, potentially linking their effects on neural plasticity with affective bias modulation in a rodent model

Rapid-acting antidepressant drugs modulate affective bias in rats

How rapid-acting antidepressants (RAADs), such as ketamine, induce immediate and sustained improvements in mood in patients with major depressive disorder (MDD) is poorly understood. A core feature of MDD is the prevalence of cognitive processing biases associated with negative affective states, and the alleviation of negative affective biases may be an index of response to drug treatment. Here, we used an affective bias behavioral test in rats, based on an associative learning task, to investigate the effects of RAADs. To generate an affective bias, animals learned to associate two different digging substrates with a food reward in the presence or absence of an affective state manipulation. A choice between the two reward-associated digging substrates was used to quantify the affective bias generated. Acute treatment with the RAADs ketamine, scopolamine, or psilocybin selectively attenuated a negative affective bias in the affective bias test. Low, but not high, doses of ketamine and psilocybin reversed the valence of the negative affective bias 24 hours after RAAD treatment. Only treatment with psilocybin, but not ketamine or scopolamine, led to a positive affective bias that was dependent on new learning and memory formation. The relearning effects of ketamine were dependent on protein synthesis localized to the rat medial prefrontal cortex and could be modulated by cue reactivation, consistent with experience-dependent neural plasticity. These findings suggest a neuropsychological mechanism that may explain both the acute and sustained effects of RAADs, potentially linking their effects on neural plasticity with affective bias modulation in a rodent model

Further validation of the affective bias test for predicting antidepressant and pro-depressant risk: effects of pharmacological and social manipulations in male and female rats

Rationale: Affective biases are hypothesised to contribute to the cause and treatment of mood disorders. We have previously found that affective biases, associated with learning and memory, are observed following acute treatments with a range of antidepressant and prodepressant manipulations.Objective: This study aimed to test if similar biases are observed in male and female Sprague Dawley (SD) rats. We also test whether the stress hormone, corticosterone induces a negative bias in the affective bias test (ABT) consistent with its putative role in the development of depression. We then use a meta-analysis to compare our findings with data published for the Lister Hooded rats.Methods: The affective bias test uses a within-subject study design where animals learn to associate distinct digging substrates, encountered on different days, with the same value food reward. Exposure to one substrate is paired with a treatment manipulation (drug or environmental) and the other with a control condition. A preference test is used to test if the treatment has induced a positive or negative bias.Results: Consistent with previous data, both male and female SD rats exhibit similar positive affective biases following treatment with the antidepressant, venlafaxine and social play and negative affective biases following FG7142 (benzodiazepine inverse agonist) and social stress. Acute treatment with corticosterone induced a negative bias.Conclusions: These data add to the translational validity of the ABT and suggest that corticosterone can induce a negative affective bias following acute treatment, an effect which may contribute to its long term effects on mood