Pharmacological Reversal of Cognitive Bias in The Chick Anxiety-Depression Continuum Model
Date of Award
M.A. in Psychology
Kenneth J. Sufka
Michael T. Allen
Cognitive bias is a phenomenon that presents in clinical populations where anxious individuals tend to adopt a more pessimistic interpretation of ambiguous aversive stimuli and depressed individuals not only tend to adopt a more pessimistic interpretation of ambiguous aversive stimuli, but also a less optimistic interpretation of ambiguous appetitive stimuli. Such biases have also been pharmacologically reversed in clinical trials. To measure cognitive bias in the chick anxiety-depression continuum model, chicks exposed to an isolation stressor of 5 min to induce an anxiety-like or 60 min to induce a depressive-like state were then tested in a straight alley maze to a series of morphed ambiguous appetitive (chick silhouette) to aversive (owl silhouette) cues. In non-isolated controls, runway start and goal latencies generally increased as a function of greater amounts of aversive characteristics in the cues. In chicks in the anxiety-like state, runway latencies were increased to aversive ambiguous cues, reflecting more pessimistic-like behavior. In chicks in the depression-like state, runway latencies were increased to both aversive and appetitive ambiguous cues, reflecting more pessimistic-like and less optimistic-like behavior, respectively. The current study sought to be able to pharmacologically reverse this cognitive endophenotype which would serve as a further validation step for the model as a neuropsychiatric simulation of anxiety and depression. Experiment 1 was conducted to ensure that drug treatments, clonidine and imipramine, do not substantially influence cognitive decision making to natural and ambiguous appetitive and aversive stimulus cues in the social treatment condition. Experiment 1 consisted of three socially tested groups (previous studies have shown that chicks tested with two cagemate conspecifics display relatively low levels of stress). Each group was administered either 0.15mg/kg clonidine (tested for 5-min indicative of the anxiety-like phase), 15mg/kg imipramine (tested for 60-min indicative of the depression-like phase), or a physiological saline (tested for 60-min to serve as the control) prior to apparatus testing. Distress vocalizations (DVocs), a dependent measure for stress, were collected for each condition. Following apparatus testing, chicks were tested immediately in the maze under four stimulus cue conditions: mirror, 25c:75o morph, 75c:25o morph: and 0c:100o (owl silhouette). To assess a baseline for each stimulus cue, a no-isolation apparatus test control group was administered saline and tested immediately within the maze. Dependent measures were start and goal latencies and farthest distance traveled and the maze cutoff criterion was 5 min. Although it was not predicted, the patterns of DVocs observed in anxiety-like and depression-like phases of socially tested chicks were consistent with previous studies in which isolated chicks exhibit a specific pattern of behavioral responses and responses to drug treatment in the anxiety-like and depression-like phases. Because differences exist in DVoc rates between drug groups for socially treated chicks, it appears that the chicks are experiencing some measurable amount of stress even within the social isolation manipulation which may be attributable to factors such as novelty to testing apparatus and flock reduction. Consistent with the modest stress patterns observed in the DVoc data, chicks exhibited a modest amount of cognitive bias within the maze, more specifically under the ambiguous stimulus cues and not the mirror or the owl stimulus cues. In general, chicks in the depression-like phase displayed more pessimistic behavior under the aversive and ambiguous aversive stimulus cues (25c:75o and 0c:100o) and also less optimistic behavior under the appetitive and ambiguous appetitive stimulus cues (mirror and 75c:25o) under mean start latency and mean distance traveled. Both forms of cognitive bias were reversed by imipramine under these two dependent measures. Although these findings were unexpected, they are consistent with the DVoc patterns observed. Given these unexpected findings the vehicle no-test group was chosen to be the main control group for experiment 2. One additional finding was that for the anxiety-clonidine group, start latencies under the mirror, 75c:25o, and 25c:75o stimulus cues were significantly shorter compared to the vehicle isolation-test group and mean distance traveled under the 25c:75o stimulus cue was significantly shorter compared to the vehicle isolation-test group. One explanation for these observed effects could be that clonidine at a dose of 0.15mg/kg produced observable sedative effects within the runway; therefore, the dose of clonidine administered in experiment 2 was decreased to 0.10mg/kg to lessen the likelihood of sedation. Experiment 2 was conducted to induce cognitive bias under an anxiety-like phase and a depression-like phase and to test whether those cognitive biases could be pharmacologically reversed. Experiment 2 followed the same procedures as experiment 1 with three exceptions: 1) a new treatment condition, a vehicle 5-min isolation group to use as a control for the anxiety-clonidine group; 2) lowering the dose of clonidine from 0.15mg/kg to 0.10mg/kg to lessen the likelihood of sedation within the runway; and 3) the induction of the isolation produce within the testing apparatus. All dependent measures remained the same. In general, chicks in the depression-like phase displayed more pessimistic behavior under the aversive and ambiguous aversive stimulus cues (25c:75o and 0c:100o) and also less optimistic behavior under the appetitive and ambiguous appetitive stimulus cues (mirror and 75c:25o) under mean start latency and mean distance traveled. Both forms of cognitive bias were reversed by imipramine under these two dependent measures. Chicks in the anxiety-like phase displayed more pessimistic behavior under the aversive and ambiguous aversive stimulus cues (25c:75o and 0c:100o) under mean start latency. However chicks that were administered clonidine tended to display sedation under mean start latency and mean distance traveled despite lowering the dose. Collectively, the observation that cognitive biases of both more pessimism and less optimism present within the single test paradigm of anxiety and depression and can be pharmacologically reversed in the depression-like phase adds to the validity of the chick anxiety-depression model as a neuropsychiatric simulation. The chick anxiety depression model, along with the runway test to ambiguous appetitive and aversive cues, may lend itself to exploring the common neurophysiological mechanisms subserving cognitive disturbances and pharmacological responses seen in these two seemingly related clinical disorders
Hymel, Kristen Anne, "Pharmacological Reversal of Cognitive Bias in The Chick Anxiety-Depression Continuum Model" (2010). Electronic Theses and Dissertations. 144.