Engagement in a non-escape (displacement) behavior elicits a selective and lateralized suppression of frontal cortical dopaminergic utilization in stress

Abstract

Although the preferential activation of the prefrontal cortical (PFC) dopaminergic system is generally observed in stress, limited exceptions to this have been observed. Certain non-escape behaviors have been demonstrated to attenuate physiological indices of stress (e.g., coping or displacement responses). One well-characterized non-escape behavior observed in stress is chewing, or gnawing, of inedible objects. Engagement in this behavior attenuates stress-related activation of the hypothalamopituitary-adrenal axis, in a variety of species. We examined the degree to which engagement in this non-escape behavior modulates stressor-induced activation of the PFC dopamine (DA) system. Rats and mice were exposed to a brightly lit novel environment (novelty stress) in the presence or absence of inedible objects. Following novelty exposure, various dopaminergic terminal fields were collected and dopamine and its major catabolite, DOPAC, were measured using HPLC with electrochemical detection. DOPAC/DA ratios were calculated as an index of DA utilization. In some cases serotonin (5-HT) and its major catabolite, 5-HIAA, were also measured. In animals that did not chew, novelty exposure elicited significant increases in DOPAC/DA levels within PFC, nucleus accumbens (shell and core subdivisions), and striatum (relative to quiet-controls). DOPAC/DA responses were greater in the right PFC than in the left PFC. Animals that chewed displayed significantly lower DOPAC/DA responses in PFC, but not other dopaminergic terminal fields. This effect of chewing was always observed in the right PFC and less consistently in the left PFC. Chewing did not alter novelty-induced increases in PFC 5-HIAA/5-HT responses. Thus, engagement in this non-escape behavior elicits a neuroanatomically and neurochemically specific attenuation of the PFC DA response in stress. Given the pivotal role of the PFC in certain cognitive and affective processes, behavioral regulation of PFC DA utilization may modulate cognitive and/or affective function in stress.

Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex

“…It is interesting to note that stress-induced increases in mPFC DA turnover were attenuated by lesions of the amygdala (Davis et al, 1994), a region known to be preferentially affected by IS but not ES (Amat et al, 1998a). The present results are also consistent with the finding that allowing organisms to engage in nonescape 'coping behaviors' such as chewing inedible objects during exposure to stress reduces mPFC DA activity (Berridge et al, 1999). Thus, it may be that a broad class of coping behaviors that attenuate the impact of stress also reduce the mPFC DA response to stress.…”

Stimulation of Lateral Septum CRF2Receptors Promotes Anorexia and Stress-Like Behaviors: Functional Homology to CRF1Receptors in Basolateral Amygdala

“…Instead, unusually long perseveration during each individual grooming episode and a concomitant elicitation of oral stereotypies were observed, suggesting that CRF 2 receptor stimulation within LS promotes prolonged expression of displacement behaviors that may interfere with the maintenance of ingestive responses. The notion that perseverative grooming and oral stereotypies are indicators of stress-like states has been proposed previously (Berridge et al, 1999); however, to the best of our knowledge, the present results provide the first evidence for the proposition that such a mechanism underlies the anorectic effects of CRF 2 receptor stimulation with LS. This proposed mechanism of CRF 2 -mediated anorexia is in agreement with a previous report demonstrating that decreases in feeding after intracerebroventricular CRF infusion were significantly correlated with stress-like behaviors such as freezing and were reversed by selective antagonism of CRF 2 receptors (Pelleymounter et al, 2000).…”

Gabaergic modulation of the stress response in frontal cortex and amygdala

“…In contrast, restrained animals that were allowed to chew during previous aversive experience performed a behavior comparable to that exhibited by control unstressed rats during the EPM exposure, suggesting that the possibility to chew in response to the aversive stimulation attenuated subsequent stress-induced aversion for open-arm activity. Similarly, neurochemical data from early reports support our behavioral observations, since chewing during different types of aversive situations reduced the activation of central catecholaminergic systems that is usually observed in response to different stressors (Tsuda et al, 1988;Berridge et al, 1999). Moreover, fighting in response to uncontrollable footshocks was clearly effective at minimizing changes in GABA A receptor binding reported to occur in shocked rats that did not have the option to fight (Cuadra and Molina, 1993).…”