Date of Graduation
Clomipramine (CLI) administered to neonatal rats has been purported to induce behavioral abnormalities in adulthood analogous to human endogenous depression (Vogel et al., 1990). Based on recent findings (e.g., Beeler, 1994; Goodman, Beeler, & Birkle, 1995), wherein CLI animals were shown to have neurobiological correlates distinct to humans diagnosed with posttraumatic stress disorder (PTSD), the current study was proposed to investigate whether CLI induced alterations might be more analogous to, and a model for, PTSD. The activity of CLI and saline control (SAL) rats across late adolescence through early adulthood (i.e., 2-, 4-, and 6 months of age) was examined in two tests of anxiety, the elevated-plus maze and acoustic startle test. Half of the rats received foot shock to investigate whether acute or chronic shock effects distinguished CLI from SAL rats. To replicate previous biological findings body weight, adrenal gland weight and plasma corticosterone levels were measured. The results of the current study showed that shock animals demonstrated behavioral suppression/anxiety and escape related open arm activity in novel testing in the elevated-plus maze. Unlike the other treatment groups, CLI/shock rats showed stable levels of anxiety across testing. In the acoustic startle test, CLI rats, overall, were most reactive with more salient arousal after repeated testing in older animals. Results of the biological measures replicated the presence of lower body and adrenal gland weights in CLI, than SAL/shock, animals. The current study did not replicate lower corticosterone levels in CLI animals with SAL/shock animal corticosterone levels higher than only the SAL control rats. The results of the present study provide support for stable anxiety levels in CLI/shock animals in a test of behavioral suppression, greater physiological reactivity in CLI animals, overall, and evidence for atypical biological responses to stress similar to the paradoxical response found for some adults with PTSD. Thus, the relevance of the present findings to PTSD, and congruity of these and previous findings with proposed animal models of PTSD (e.g., Yehuda and Antelman, 1993), suggests that CLI induced PTSD as an animal model of PTSD, warrants further investigation.
Beeler, Linda Louise, "A proposed animal model of clomipramine-induced posttraumatic stress disorder." (1997). Graduate Theses, Dissertations, and Problem Reports. 8460.