Role of the central nucleus of the amygdala in hemodynamic responses to cocaine in conscious rats.

Abstract

The central nucleus of the amygdala (CeA) has been shown to play an important role in sympathetic and behavioral responses to stress. We observed a greater vasoconstrictor response to cocaine in some rats (vascular responders or VR) compared to other rats (mixed responders or MR). We hypothesized that the CeA was responsible for greater increases in systemic vascular resistance (SVR) in response to cocaine and that angiotensin II (Ang) and corticotropin‐releasing factor (CRF) receptors were involved. Rats were instrumented for arterial pressure and cardiac output determination and for drug microinjection into the CeA. Rats were given cocaine (5 mg/kg, iv, twice daily, 4X) to determine their response pattern (VR or MR). Subsequently, rats were pretreated with bilateral microinjections (100 nl) of saline, muscimol (80 pmol), losartan (20 ng), or á‐helical‐CRF9‐41 (60 ng) followed by cocaine. Pretreatment with muscimol or losartan attenuated the increase in systemic vascular resistance (SVR) evoked by cocaine. Pretreatment with CRF antagonist prevented the difference in responsiveness between MR and VR by increasing the increase in SVR in MR. Our data suggests that the greater increases in SVR in vascular responders depend on neuronal transmission in the CeA and that Ang receptors facilitate and CRF receptors inhibit SVR responses to cocaine administration. Supported by USPHS RO1 DA13256 and DA0017371.