Dissociation in control of physiological and behavioral responses to emotional stress by cholinergic neurotransmission in the bed nucleus of the stria terminalis in rats

Abstract

The bed nucleus of the stria terminalis (BNST) is a forebrain structure implicated in physiological and behavioral responses to emotional stress. However, the local neurochemical mechanisms mediating the BNST control of stress responses are not fully known. Here, we investigated the involvement of BNST cholinergic neurotransmission, acting via muscarinic receptors, in cardiovascular (increase in blood pressure and heart rate and fall in tail skin temperature) and neuroendocrine (increase in plasma corticosterone) responses and behavioral consequences (anxiogenic-like effect in the elevated plus-maze) evoked by acute restraint stress in rats. Bilateral microinjection into the BNST of either the choline uptake inhibitor hemicholinium-3 (3 nmol/100 nl) or the muscarinic receptor antagonist methylatropine (3 nmol/100 nl) enhanced the heart rate increase and inhibited the anxiogenic-like effect observed in the elevated plus-maze evoked by restraint. However, neither hemicholinium-3 nor methylatropine affected the increase in blood pressure and plasma corticosterone levels and the fall in tail skin temperature. Facilitation of local cholinergic signaling by microinjection of the acetylcholinesterase inhibitor neostigmine (0.1 nmol/100 nl) into the BNST reduced restraint-evoked pressor and tachycardiac responses and the fall in tail cutaneous temperature, without affecting the increase in plasma corticosterone. All effects of neostigmine were completely abolished by local BNST pretreatment with methylatropine. These findings indicate an opposite role of BNST cholinergic neurotransmission, acting via local muscarinic receptor, in control of cardiovascular responses (inhibitory influence) and emotional consequences (facilitatory influence) evoked by restraint stress. Furthermore, present findings provide evidence that BNST control of neuroendocrine responses to stress is mediated by mechanisms others than local cholinergic signaling.

Involvement of endocannabinoid neurotransmission in the bed nucleus of stria terminalis in cardiovascular responses to acute restraint stress in rats

“…The majority of CB 1 receptors are expressed on axon terminals, and their activation suppresses the release of other neurotransmitters into the synapse (Katona and Freund, ). Previous studies reported that local BNST treatment with either an α 1 ‐adrenoceptor antagonist or a muscarinic ACh receptor antagonist enhanced the restraint‐evoked HR increase (Crestani et al , ; Gouveia et al , ). Additionally, a recent study documented that microinjection of corticotropin‐releasing factor (CRF) receptor antagonists into the BNST reduced cardiovascular responses to restraint (Oliveira et al , ).…”

“…The cutaneous temperature of the tail was recorded using a thermal camera (IRI4010, Infra Red Integrated Systems Ltd., Northampton, UK). The temperature was measured on five points of the animal's tail and the mean value was calculated for each recording (Vianna and Carrive, ; Cruz et al , ; Gouveia et al , ).…”

“…The needles (33G, Small Parts, Miami Lakes, FL, USA) used for microinjection into the BNST were 1 mm longer than the guide cannulae and were connected to a 2μL syringe (7002‐KH, Hamilton Co., Reno, NV, USA) using a PE‐10 tubing (Clay Adams, Parsippany, NJ, USA). Needles were carefully inserted into the guide cannulae without restraining the animals, and drugs were injected in a final volume of 100 nL (Crestani et al , ; Gomes et al , ; Gouveia et al , ).…”

Dual role of nitrergic neurotransmission in the bed nucleus of the stria terminalis in controlling cardiovascular responses to emotional stress in rats

“…Therefore, the modulation of restraint-evoked pressor response by nitrergic neurotransmission in the BNST seems to be mediated by mechanisms other than local noradrenergic neurotransmission. One possible option is cholinergic neurotransmission, as activation of muscarinic receptors in the BNST inhibited the cardiovascular responses to restraint stress (Gouveia et al, 2016). Although there are reports of an NO-induced release of acetylcholine in limbic structures such as the hippocampus and prefrontal cortex (Ohkuma and Katsura, 2001;Prast and Philippu, 2001), a possible interaction between nitrergic and cholinergic neurotransmissions within the BNST has never been evaluated.…”

Sex differences in cardiovascular, neuroendocrine and behavioral changes evoked by chronic stressors in rats

“…The elevated plus maze (EPM) test was conducted as described before (Gouveia et al, 2016;Padovan and Guimaraes, 2000). Briefly, the apparatus consisted of two opposite open arms [(50 cm (length) × 10 cm (width) × 0.25 cm (height)] crossed at a right angle by two arms of the same dimensions enclosed by 40 cm high walls with no roof.…”