Abstract
The neuropsychological hypothesis of depression suggests that negative affective biases are linked to the development and maintenance of MDD symptoms as well as to the mechanisms underlying the effects of antidepressant drugs. It has been previously shown that conventional and rapid-acting antidepressants differ in their ability to modify affective biases related to learning and memory in the rodent affective bias test (ABT). This thesis investigates the effects of both amitriptyline, a tricyclic antidepressant, and (2R, 6R) hydroxynorketamine (HNK), a ketamine metabolite, on the formation of affective biases toward new reward- paired associations as well as on the modulation of previously established negative affective biases using the ABT. In addition, the effects of both drugs on reward-induced biases were tested using a rodent reward learning assay (RLA).The ABT studies revealed that acute treatment with amitriptyline was able to positively bias learning of new reward-paired associations while HNK failed to demonstrate an effect on new learning. However, both amitriptyline and HNK were able to attenuate the retrieval of previously learnt negative affective biases in the ABT following acute administration. When tested 24 hours post-treatment, animals treated with HNK exhibited a positive bias toward the stimulus that had been previously paired with the negative affective state manipulation. Neither amitriptyline nor HNK had an effect on the formation of reward-induced biases in the RLA, suggesting that their effects are specific to biases related to affective state.
To further explore the emotional complexity of rodents, this thesis also investigated the extent to which rats demonstrate self-directed behavior in an olfactory self-recognition task. Research has shown that species known to fail vision-based measures of self-awareness may demonstrate self-directed behavior if the task caters to the primary sensory modality of that species. The experiment discussed here found that rats exhibited greater exploration of both their own scent and that of a conspecific when the conspecific’s scent held a greater degree of novelty, suggesting that rats may possess social awareness rather than an introspective “self- awareness.”
In summary, these results provide further evidence of the neuropsychological mechanisms associated with affective biases as well as those underlying the effects of both conventional and rapid-acting antidepressants. In addition, the results of the olfactory recognition study allow for further understanding of the cognitive capabilities of laboratory rodents which may inform both laboratory animal welfare practices as well as the preclinical study of depression and other mood disorders.
| Date of Award | 9 May 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Ingeborg Hers (Supervisor) & Emma S J Robinson (Supervisor) |