Anxiogenic-like effects of fluoxetine render adult male rats vulnerable to the effects of a novel stress

作者：Gomez Francisca^*; Garcia Garcia Luis

来源：Pharmacology Biochemistry and Behavior, 2017, 153: 32-44.

DOI：10.1016/j.pbb.2016.12.007

• Fluoxetine
• Stress
• Stress-induced hyperthermia
• Hypothalamic-pituitary-adrenal axis
• CRH
• POMC
• Arcuate nucleus
• Behavior
• Anxiety
• Food intake
• Body weight
• Energy homeostasis

Fluoxetine (FLX) has paradoxical anxiogenic-like effects during the acute phase of treatment. In adolescent (35 Bold) male rats, the stress-like effects induced by short-term (3 d-4 d) FLX treatment appear to involve up-regulation of paraventricular nucleus (PVN) arginine vasopressin (AVP) mRNA. However, studies on FLX-induced anxiety-like effects in adult rodents are inconclusive. Herein, we sought to study the response of adult male rats (60-65 d-old) to a similar FIX treatment, also investigating how the stressful component, inherent to our experimental conditions, contributed to the responses. We show that FIX acutely increased plasma corticosterone concentrations while it attenuated the stress-induced-hyperthermia (SIH) as well as it reduced (approximate to 40%) basal POMC mRNA expression in the arcuate nucleus (ARC). However, FIX did not alter the basal expression of PVN-corticotrophin-releasing hormone (CRH), anterior pituitary-pro-opiomelanocortin (POMC) and raphe nucleusserotonin transporter (SERT). Nonetheless, some regressions point towards the plausibility that FIX activated the hypothalamic-pituitary-adrenal (HPA). The behavioral study revealed that FIX acutely increased emotional reactivity in the holeboard, effect followed by a body weight loss of approximate to 2.5% after 24 h. Interestingly, i.p. injection with vehicle did not have behavioral effects, furthermore, after experiencing the stressful component of the holeboard, the rats kept eating and gaining weight as normal. By contrast, the stress-naive rats reduced food intake and gained less weight although maintaining a positive energy state. Therefore, on one hand, repetition of a mild stressor would unchain compensatory mechanisms to restore energy homeostasis after stress increasing the resiliency to novel stressors. On the other hand, FIX might render stressed adult rats vulnerable to novel stressors through the emergence of counter-regulatory changes, involving HPA axis activation and diminished sympathetic output may be due to reduced melanocortin signaling. Therefore, complex interactions between hypothalamic CRH and POMC might be determining the adaptive nature of the response of adult male rats to FIX and/or stress.

• 出版日期2017-2