Sensitization to Stressors

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In experimental animals and in humans, single or sporadic exposure to certain stimuli including stressors, immune activation, and drugs of abuse can result in long-lasting (weeks-lifetime) sensitization. Although the information is scarce, the mechanisms underlying long-lasting sensitization may be different from sensitization seen during chronic or repeated stimulation (Antelman & Caggiula, 1996). In most chronic or repeated stress protocols that lead to sensitization, the neurochemical, behavioral, metabolic, and neuroendocrine responses undergo progressive alterations during stress exposure, and tend to return to their pre-stress profiles after cessation of the stress load (Van Dijken, 1992). Therefore, we and others have looked upon such chronic stress induced alterations as an effect of cumulation of rather short term effects (De Goeij, Binnekade, & Tilders, 1992a). Long-lasting sensitization by a single event follows a different pattern. For instance, exposure of adult rats to a single and short (15min) session of electric foot shocks induces behavioral sensitization to novel stressors, which progressively develops to reach a maximum approximately two weeks after the challenge (Van Dijken, Van Der Heijden, Mos, & Tilders, 1992c), and can be maintained for two months as illustrated in Fig l.Thus, behavioral sensitization can develop in the absence of further stimuli.

Because this pattern of behavioral sensitization is paralleled by sensitization of neuroendocrine and autonomic stress responses (Antelman, De Giovanni, & Kocan, 1989, Fig IB, 1C), this form of long- lasting stress sensitization may reflect a state of increased stress vulnerability as seen in various psychiatric disorders (Akil & Ines Morano, 1995). In support of this, footshock-induced long-lasting behavioral sensitization was associated with increased anxiety related behavior, and anxiolytics were found to reverse these aberrant responses (Van Dijken, Mos, Van Der Heijden, & Tilders, 1992a; Van Dijken, Tilders, Olivier, & Mos, 1992b). Several other stressors including social defeat have been reported to induce alterations in behavioral and metabolic parameters that last for a week or more (Meerlo, Overkamp, & Koolhaas, 1997; Sherman & Petty 1982). Thus, although the effects of most stressors on subsequent responses dissipate within a few days, certain stressful events appear to provoke progressive and long-lasting alterations in stress responsive brain circuits that has precipitated in the "Once is enough" hypothesis (Van Dijken, 1992).

There is a large body of literature on long-lasting effects of perinatal stress exposure on stress vulnerability, stress responses and changes in brain stress circuits. Collectively, these observations show that the developing organism is extremely

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