Cardiovascular and respiratory responses to a panicogenic agent in anaesthetised female Wistar rats at different stages of the oestrous cycle

Abstract

In urethane-anaesthetised female Wistar rats, intravenous injection of the panicogenic CCK(B) receptor agonist pentagastrin (0.002-80 microg/kg) evoked a dose-related increase in blood pressure, heart rate and ventilation. The response was blocked in the presence of the selective CCK(B) receptor antagonist CR2945 (1 mg/kg i.v.). The same pattern of cardiovascular and respiratory changes was evoked by microinjection of pentagastrin (0.3 nmol in 250 nL) into the dorsal half of the periaqueductal grey matter (PAG). The effect of intra-PAG administration of pentagastrin was also abolished following injection of CR2945 (1 mg/kg, i.v.). Responsiveness to systemically administered pentagastrin was enhanced in rats in late dioestrus. At the highest dose tested (80 microg/kg), the pressor response, tachycardia and tachypnoea evoked in rats in late dioestrus was significantly higher than rats in proestrus. For rats in oestrus, the pressor response and tachycardia but not tachypnoea were also significantly larger than the response evoked in rats in early dioestrus. The results suggest that the dorsal half of the PAG (dPAG) plays a key role in mediating the cardiovascular and respiratory responses evoked by systemically administered CCK(B) agonists. The enhanced responsiveness to panicogenic agents during late dioestrus may be related to changes in the functional responsiveness of gamma-aminobutyric acid (GABA)ergic circuitry in the dPAG due to plasticity of GABA(A) receptor subunit expression as a consequence of falling progesterone levels.