Research reportSensitization of norepinephrine release in medial prefrontal cortex: effect of different chronic stress protocols
Introduction
Chronic exposure to stress can alter the activity of locus coeruleus (LC) noradrenergic neurons (for review see Refs. 37, 42). For example, prolonged exposure to stress may increase the response of LC neurons to subsequent presentation of a stressor. Specifically, we have found that rats previously exposed to cold (5°C) for 2–4 weeks exhibit a greater increase in extracellular norepinephrine (NE) in hippocampus and medial prefrontal cortex (mPFC) in response to acute tail shock 14, 18, 31. We have referred to this phenomenon as stress-induced sensitization of NE release. At present, it is not known whether sensitization of NE release occurs following exposure to chronic stressors other than cold. However, several findings suggest that this phenomenon may be induced by a variety of chronic stress protocols. These include the observation that (1) prior exposure to foot shock potentiated the foot shock-evoked increase in NE turnover 6, 20, 38, (2) prior exposure to restraint potentiated the immobilization-evoked decrease in tissue NE levels [4], and (3) prior exposure to tail shock potentiated the increase in firing rate of LC neurons elicited by paw compression [35]. An increase in LC firing rate evoked by sciatic nerve stimulation also has been observed following chronic cold exposure [28]. Furthermore, stress-induced sensitization of catecholamine release also has been described in the sympathoadrenal system. Presentation of a novel stressor elicited a greater increase in NE release from the adrenal medulla following chronic exposure to either swim stress, restraint, or foot shock [26]. Together, these findings suggest that the stress-evoked activity of central and peripheral noradrenergic systems may be increased following exposure to a variety of chronic stress protocols.
In an initial study, we examined whether sensitization of NE release occurs following exposure to repeated intermittent foot shock. This stressor was chosen because it is one of the most commonly used chronic stress protocols in the literature. Contrary to our hypothesis that sensitization would generalize to other chronic stressors, we observed that repeated intermittent exposure to foot shock for 2 weeks did not result in sensitization of NE release in the mPFC [21]. Thus, our studies indicate that sensitized NE release is expressed in the mPFC following 2 weeks of continuous exposure to cold but not following 2 weeks of repeated intermittent exposure to foot shock. We have now examined whether the pattern of exposure to the chronic stressor (continuous or intermittent), the nature of the chronic stressor (cold or foot shock), or both are determinants in the development of sensitized NE release. Thus, in the present studies rats were exposed either intermittently or continuously to either cold or foot shock. In vivo microdialysis was then used to examine basal and tail shock-evoked extracellular NE concentrations in the mPFC.
Section snippets
Animals
Upon arrival, male Sprague–Dawley rats (Zivic-Miller, Zelienople, PA) weighing 150–175 g were housed singly in hanging stainless steel cages in a colony room maintained at an ambient temperature of 23°C. Throughout the experiments, lights were maintained on a 12 h light–dark cycle (lights on at 0800 h), and food (Laboratory rodent diet 5001, PMI Feeds, St. Louis, MO) and water were available ad libitum. All rats remained undisturbed in the colony room for 5–10 days prior to any treatment. Rats
Effect of continuous and repeated intermittent cold exposure on extracellular NE concentrations in mPFC
Basal extracellular NE concentrations in the mPFC were not affected by exposure to cold for 4 h/day for 14 days or continuously for 14 days (Fig. 1). Thirty minutes of acute tail shock significantly increased extracellular NE in the mPFC of control rats as well as intermittent and continuous cold rats. However, the magnitude of this increase varied across the three groups [F(6,90)=5.40, p<0.01]. In control rats, tail shock elicited a 115±12% increase in extracellular NE in the mPFC. Similarly,
Discussion
Previously, we reported that rats continuously exposed to cold for 14 days or longer exhibit an enhanced tail shock-evoked increase in extracellular NE in the mPFC 14, 18. We have now examined whether sensitization of NE release occurs in response to chronic stress protocols other than continuous cold exposure. Results of the present studies indicate that whereas sensitization of evoked NE release occurs following continuous cold exposure, it is not expressed following a continuous foot shock
Acknowledgements
This research was supported by U.S. Public Health Service grants MH29670 and MH45156.
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