Cholinergic Influences on Hypothalamic-Pituitary-Adrenocortical Activity of Stressed Rats: An Approach Utilizing Agonists and Antagonists

Abstract

Cholinergic involvement in the regulation of the hypothalamic-pituitary\x=req-\ adrenocortical (HPA) system of male rats was evaluated using muscarinic (atropine and methacholine) and nicotine (mecamylamine and nicotine) agents, which were selected for their specificity on cholinergic receptors (ChR). They were administered either intracerebroventricularly (icv) to produce central effects, or ip to produce both central and peripheral effects, prior to subjecting the animals to either auditory or hypercapnic stress for 1 h. Plasma corticosterone was used as an index of HPA activity. The results suggest that central muscarinic ChR are involved in inhibiting HPA activity in both non-stressed and stressed animals, whereas central nicotinic ChR are excitatory during stress but inactive in the non\x=req-\ stressed state. Stimulation of peripheral nicotinic ChR appeared to potentiate the HPA response to hypercapnia, and to inhibit the central excitatory nicotinic ChR when the latter were activated in non-stressed and auditory stressed rats. These data suggest that during auditory stress the HPA system is more dependent upon the cholinergic system for its activation than during non-stressed and hypercapnic states.It is well known that the nervous system greatly influences the basal, rhyth¬ mic and stressful activities of the hypothalamic-pituitary-adrenocortical ( ) system. Recently, chemical stimulation and/or blockade of catecholaminergic, serotonergic and gabanergic receptors have been employed to further clarify

Nicotinic acetylcholine receptors as targets for antidepressants

“…84 Involvement of nAChR during stress is implicated by the observation that chronic stress causes a downregulation of nAChR in the brain. 85 Direct involvement of nicotinic receptor activation in contributing to the neuroendocrine responses to stress is supported by the finding that mecamylamine abolishes the plasma corticosterone response to auditory stress in rats 86 and has anxiolytic properties in animal models. 87 Physiologically, nicotinic receptor blockade reduces the effects of stress on cardiovascular function 88 and inhibits emotionally conditioned presser responses in rats.…”

Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulb

“…Acute-stress-induced increases in glucocorticoids, in which the BFC afferent to the hippocampus functions as an important negative-feedback system (Sithichoke & Marotta 1978;Han et al 2002;Helm et al 2002), are reportedly involved in the stressinduced decrease in cell-proliferation (Cameron et al 1995;Gould et al 1997;Tanapat et al 2001). However, the mechanisms underlying the inhibition of neurogenesis caused by chronic stress remain unknown.…”

Muscarinic Agonist-Mediated Increases in Serum Corticosterone Levels Are Abolished in M2 Muscarinic Acetylcholine Receptor Knockout Mice

“…Muscarinic agonists have been shown to stimulate the hypothalamic-pituitary-adrenocortical axis (HPA) axis via central corticotropin-releasing hormone release (Hedge and De Wied, 1971;Sithichoke and Marotta, 1978;Calogero et al, 1989;Bugajski et al, 1998). The muscarinic receptor subtype mediating corticotropin-releasing hormone secretion and subsequent stimulation of the HPA axis, however, has not been established.…”