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.…”

Hypocretin/Orexin Selectively Increases Dopamine Efflux within the Prefrontal Cortex: Involvement of the Ventral Tegmental Area

“…This procedure was based on previous observations indicating that slow implantation results in substantially higher extracellular levels of norepinephrine and DA within the PFC relative to rapid insertion via an indwelling cannula. The magnitude of stressor-induced activation of DA efflux within the PFC and Acc estimated with these procedures is comparable to that observed with both postmortem measures and dialysis probe implantation 7 days following surgical implantation of a guide cannula (Abercrombie et al, 1989;Berridge et al, 1999a;Feenstra et al, 2000). Moreover, the magnitude of HCRT-induced waking observed following only 1-2 days recovery from surgery in the current studies was comparable to previous observations in animals given a recovery period of at least 7 days (España et al, 2001).…”

“…Although we did not observe an increase in Acc DA levels after either ICV or intra-VTA HCRT infusion, it has been well established by our laboratory and others that such an increase can occur under similar experimental conditions (Westerink et al, 1996;Ikemoto et al, 1997;Berridge et al, 1999aBerridge et al, , 2003.…”

Fear and Feeding in the Nucleus Accumbens Shell: Rostrocaudal Segregation of GABA-Elicited Defensive Behavior Versus Eating Behavior

“…Aside from its role in positive appetitive behavior, the accumbens shell has also been implicated in negative motivational states, such as stress, fear, and defensive behavioral responses elicited by noxious or threatening stimuli (Inoue et al, 1994;Beck and Fibiger, 1995;Gray, 1995;Salamone et al, 1997;Berridge et al, 1999;Liberzon et al, 1999). Footshock increases extracellular dopamine in the accumbens shell but not core (Kalivas and Duff y, 1995), and increased accumbens dopamine or DOPAC have also been reported after other noxious stimuli, such as tail pinch, anxiogenic drugs, bright novel environments, or immobilization stress (Thierry et al, 1976;D'Angio et al, 1987;Bertolucci-D'Angio et al, 1990;McCullough and Salamone, 1992;Berridge et al, 1999).…”

“…Footshock increases extracellular dopamine in the accumbens shell but not core (Kalivas and Duff y, 1995), and increased accumbens dopamine or DOPAC have also been reported after other noxious stimuli, such as tail pinch, anxiogenic drugs, bright novel environments, or immobilization stress (Thierry et al, 1976;D'Angio et al, 1987;Bertolucci-D'Angio et al, 1990;McCullough and Salamone, 1992;Berridge et al, 1999). Even conditioned stimuli for fear, such as auditory or context cues that have been paired with shock, may produce increases in accumbens dopamine and accumbens Fos expression (Beck and Fibiger, 1995;Young et al, 1998).…”