Abstract

Exposure of animals to noxious or stressful stimuli increases heart rate (HR) and blood pressure through activation of the autonomic nervous system (ANS). Stressors also elicit the release of the neuromodulatory catecholamines dopamine (DA) and noradrenaline (NA) in several regions of the forebrain. Although many of these regions project to brainstem nuclei involved in the control of autonomic output, the functions of the catecholamines in the modulation of responses to stressful stimuli mediated by the ANS are not known. To resolve this issue, a series of experiments was carried out to examine the effects of injections of agonists, and antagonists of DAergic and NAergic receptors into four regions of the forebrain innervated by the catecholaminergic projections, on an autonomically-mediated response to stress, the increase in HR induced by tail pinch, in rats anesthetized with urethane. The regions tested included the medial frontal cortex (MFC), agranular insular cortex (AIC), nucleus accumbens (NAC) and the central nucleus of the amygdala (CeA). Injections of an antagonist of Ý-adrenoceptors into each of these regions reduced the magnitude of the increase in HR induced by tail pinch. Injections of an agonist of Ý-adrenoceptors in the MFC, AIC and NAC increased basal HR but did not affect the pinch response. Injections of drugs acting at Ì-adrenoceptors altered neither of these parameters, but injections of a combination of agonists of Ì- and Ý-adrenoceptors made into the NAC markedly increased the magnitude of the response to pinch. When injected alone, agonists or antagonists of DAergic receptors were largely without effect on basal HR and the response to pinch. However, injections of a combination of a D 2 antagonist and an agonist of the Ý-adrenoceptor into the AIC significantly increased the magnitude of the pinch response. These results provide the first clear evidence that catecholamines released in the forebrain during basal conditions and in response to stress are important modulators of autonomic output. NA, primarily through actions on Ý-adrenoceptors, exerts the most salient influence, serving to facilitate the output of the ANS during both of these conditions. In the case of the NAC, this NAergic influence may be facilitated, in turn, by the stimulation of Ì-adrenoceptors. Although DA in these regions may not have a salient influence on autonomic output, it may, via the stimulation of D 2 receptors, modulate the actions of NA on Ý-adrenoceptors in at least the AIC.