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.