Angiotensin II and CRF receptors in the central nucleus of the amygdala mediate hemodynamic response variability to cocaine in conscious rats

Abstract

Stress or cocaine evokes either a large increase in systemic vascular resistance (SVR) or a smaller increase in SVR accompanied by an increase in cardiac output (designated vascular and mixed responders, respectively) in Sprague-Dawley rats. We hypothesized that the central nucleus of the amygdala (CeA) mediates this variability. Conscious, freely-moving rats, instrumented for measurement of arterial pressure and cardiac output and for drug delivery into the CeA, were given cocaine (5 mg/kg, iv, 4-6 times) and characterized as vascular (n=15) or mixed responders (n=10). Subsequently, we administered cocaine after bilateral microinjections (100 nl) of saline or selective agents in the CeA. Muscimol (80 pmol), a GABA A agonist, or losartan (43.4 pmol), an AT 1 receptor antagonist, attenuated the cocaine-induced increase in SVR in vascular responders, selectively, such that vascular responders were no longer different from mixed responders. The corticotropin releasing factor (CRF) antagonist, α-helical CRF 9-41 (15.7 pmol), abolished the difference between cardiac output and SVR in mixed and vascular responders. We conclude that greater increases in SVR observed in vascular responders are dependent on AT 1 receptor activation and, to a lesser extent on CRF receptors. Therefore, AT 1 and CRF receptors in the CeA contribute to hemodynamic response variability to intravenous cocaine.

Stress-induced changes in c-Fos and corticotropin releasing hormone immunoreactivity in the amygdala of the spontaneously hypertensive rat

“…The present study is the first to evaluate CRH protein levels in the amygdala of the SHR and the results demonstrate that similar to the PVN, CRH expression in the CEA is significantly elevated in response to AJS and neuronal CRH expression is greater in the caudal CEA of the SHR compared to the Wistar strain. Although there is strong evidence that modulation of CRH expression in the amygdala can occur in response to acute stress (33) and is critical for both the behavioral expression of fear (33, 37) and autonomic responses to both stressful (72) and non-stressful stimuli (73), additional studies are needed to fully evaluate how stress-induced changes in CRH protein expression in the CEA contribute to the exaggerated autonomic response to stress reported here in the SHR.…”

Korean Red Ginseng attenuates anxiety-like behavior during ethanol withdrawal in rats

“…Imbalances between inhibitory and excitatory systems in the brain during EW, including hypoactivation of the GABAergic system but hyperactivation of the glutamatergic system, a deficiency of DA but excessive release of norepinephrine, and the downregulation of neuropeptide Y but upregulation of corticotrophin releasing factor, are the main causative factors underlying EW-induced anxiety [7,19] . Of these factors, DA deficiency in the CeA appears to be the most critical, because the mesoamygdaloid DA system is a convergent site wherein the effects of the positive and negative reinforcement of ethanol are processed [20,21] . Therefore, in the present study, the mesoamygdaloid DA system was selected as a principal site in which to investigate the underlying mechanisms of the anxiolytic effects of KRGE.…”

A previous history of repeated amphetamine exposure modifies brain angiotensin II AT1 receptor functionality

“…It is known that brain ANG II regulates some responses induced by drugs of abuse such as cocaine and amphetamine (Hosseini et al, 2007;Watanabe et al, 2010;Paz et al, 2011Paz et al, , 2013. It has been described that ANG II can markedly potentiate DA release in CPu projecting dopaminergic neurons involving pre-and post-synaptic mechanisms (Mendelsohn et al, 1993;Brown et al, 1996) and in NAc (Hoebel et al, 1994).…”