Monoaminergic influences on the regulation of the hypothalamo-hypophyseal-adrenocortical (HHA) system during acute stresses (hypoxia and hypercapnia) were investigated in male rats. Plasma corticosterone levels were used to assess HHA activity, and the alterations in monoaminergic activity were induced by pretreating the animals with various pharmacologic agents (reserpine, αMT, FLA-63, pCPA, L-Dopa, pargyline, Lilly 110140, phentolamine and propranolol). Dexamethasone-treated rats were utilized to assess the site at which these monoaminergic substances acted. The latter experiments showed that these agents did not have a marked effect directly on the adrenal cortex and thus the site(s) of action was at the level of the anterior pituitary and/or above. Altering the serotoninergic system did not appreciably influence the HHA response to hypoxia and hypercapnia, whereas increasing the activity of the adrenergic system partially prevented the rise usually observed in plasma corticosterone levels during these stresses. These data suggest that different aminergic pathways may be utilized for different stresses.

Adrenergic (α and β), cholinergic (m and n) and gabanergic (γ) influences on the regulation of basal hypothalamo-hypophyseal-adrenocortical (HHA) activity, as assessed by plasma cortisol levels, were investigated in non-stressed conscious cats. Alterations in neurotransmitter activities were induced by perfusing the cerebroventricles for 60 min with mock cerebrospinal fluid containing α, β, m, n and γ antagonists given alone or in various combinations. Neither γ, m nor n blockers altered basal HHA activity, whereas both α and β blockers given alone or together, or combined with m, n and γ blockers markedly elevated plasma cortisol. These responses were inhibited by the addition of dexamethasone to the perfusion fluid. These data suggest that basal HHA activity in the cat is maintained by a central inhibitory action of the adrenergic system on spontaneously discharging corticotropin-releasing factor neurons, and not via an adrenergic-cholinergic-gabanergic neural chain.

The effects of altering the concentrations of various cerebrospinal fluid (CSF) cations on hypothalamo-hypophyseal-adrenocortical (HHA) activity were investigated in conscious cats. The cerebroventricles were perfused with CSF containing high or low [Na+], [K+], [Li+], [Ca²+] and [Mg²+] for 60 min and plasma samples taken periodically for analysis of cortisol. The results demonstrate that changing CSF [Na+] or [Li+] does not substantially alter plasma cortisol levels. Although individually elevating CSF [K+], [Ca²+] or [Mg²+] does not affect plasma cortisol levels, reducing these CSF cations activates the HHA system and the latter in turn is inhibited by the addition of dexamethasone (DEX) to low cation CSF. The excitatory action of reduced [Ca²+] is also inhibited by the addition of norepinephrine to the perfusion fluid, suggesting that lowering this cation affects the HHA system by preventing the release of the adrenergic neurotransmitter. Furthermore, these data suggest that in conscious unrestrained cats basal HHA activity is dependent to some extent upon normal brain extracellular [K+], [Ca²+] and [Mg²+].