γ-Hydroxybutyric acid induces actions via the GABAB receptor in arousal and motor control-related nuclei: Implications for therapeutic actions in behavioral state disorders

Kohlmeier, Kristi A.; Vardar, Bige; Christensen, Mark H.

doi:10.1016/j.neuroscience.2013.06.011

Cited by 20 publications

(19 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, single cell calcium imaging in which the calcium indicator was loaded via the intracellular pipette showed a baclofen-induced decrease in depolarization-induced rises in intracellular calcium (Kohlmeier & Kristiansen, 2010). A follow-up calcium imaging study using multiple cell imaging similar to that utilized in the present examination, showed that the application of baclofen or γ-hydroxybutyric acid (GHB, a putative GABA B R-agonist) was associated with decreases and increases in baseline levels of calcium (Kohlmeier et al, 2013). Evidence has also been presented for the functional presence of GABA Aρ R in the LDT using monitoring of membrane currents following receptor stimulation (Kohlmeier & Kristiansen, 2010 However, whether elicitation of changes in intracellular calcium reflected as alterations in F/F 0 following agonism at the ionotropic GABA A R and the subclass of the GABA Aρ R, would occur was uncertain.…”

Section: Responses In Calcium In the Ldt Elicited By The Three Knowmentioning

confidence: 50%

“…In a previous study, we had shown that GABA B stimulation results in changes in florescence in LDT neurons, and both decreases and increases in fluorescence could be elicited (Kohlmeier, Vardar, & Christensen, 2013). We have replicated and extended those findings here, as we found that changes in fluorescence were elicited by baclofen in the majority of the cells in the two age groups in either sex and in both treatments, and baclofen elicited changes in F/F 0 which were suggestive of both decreases and increases in calcium (Figure 3a1,2).…”

Section: Pne Was Associated With Alterationsmentioning

confidence: 94%

“…Therefore, alterations in GABAergic neurotransmission within the LDT could contribute to aversive effects on behavioral and cognitive outcomes associated with PNE that are suspected to involve alterations in mesocorticolimbic and thalamocortical processing (Cornelius & Day, 2009;Dwyer et al, 2009;Kohlmeier, 2015;Lacy et al, 2014;Paz et al, 2007;Smith et al, 2010). Although alterations in GABAergic-mediated transmission from the LDT have not been shown to play a crucial role in PNE-associated negative behavioral outcomes, GABARs within the mesopontine tegmentum have been suggested to play a role in the mediation of behaviors and emotion via their presence on mesoaccumbal, mesocortical and thalamic LDT projection neurons (Arnaud, Gauthier, & Gottesmann, 2001;Braun et al, 1997;Kantrowitz, Citrome, & Javitt, 2009;Kohlmeier et al, 2013;Maquet et al, 1996). Further, in rat retina, GABA A -ρR has been proposed to inhibit the release of ACh which suggests that alterations in GABA A -ρR functioning within the LDT could play a role specifically within the cholinergic projections leading to alterations in ACh release to target regions known to be critical in arousal and motivated behaviors (Dautan et al, 2016;Massey, Linn, Kittila, & Mirza, 1997).…”

Section: Functional Significancementioning

confidence: 99%

See 2 more Smart Citations

Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine

Eliasen

Krall

Frølund

et al. 2020

Developmental Neurobiology

View full text Add to dashboard Cite

Smoking during pregnancy is associated with deleterious physiological and cognitive effects on the offspring, which are likely due to nicotine‐induced alteration in the development of neurotransmitter systems. Prenatal nicotine exposure (PNE) in rodents is associated with changes in behaviors controlled in part by the pontine laterodorsal tegmentum (LDT), and LDT excitatory signaling is altered in a sex and age‐dependent manner by PNE. As effects on GABAergic LDT signaling are unknown, we used calcium imaging to evaluate GABAA receptor‐ (GABAAR as well as GABAA‐ρR) and GABAB receptor (GABABR)‐mediated calcium responses in LDT brain slices from female and male PNE mice in two different age groups. Overall, in older PNE females, changes in calcium induced by stimulation of GABAAR and GABABR, including GABAA‐ρR were shifted toward calcium rises. In both young and old males, PNE was associated with alterations in calcium mediated by all three receptors; however, the GABAAR was the most affected. These results show for the first time that PNE is associated with alterations in GABAergic transmission in the LDT in a sex‐ and age‐dependent manner, and these data are the first to show PNE‐associated alterations in functionality of GABA receptors in any nucleus. PNE‐associated alterations in LDT GABAergic transmission within the LDT would be expected to alter output to target regions and could play a role in LDT‐implicated, negative behavioral outcomes following gestational exposure to smoking. Accordingly, our data provide further supportive evidence of the importance of eliminating the consumption of nicotine during pregnancy.

show abstract

Section: Responses In Calcium In the Ldt Elicited By The Three Knowmentioning

confidence: 50%

Section: Pne Was Associated With Alterationsmentioning

confidence: 94%

Section: Functional Significancementioning

confidence: 99%

See 1 more Smart Citation

Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine

Eliasen

Krall

Frølund

et al. 2020

Developmental Neurobiology

View full text Add to dashboard Cite

show abstract

“…Carbachol also caused an outward current which was not observed in the presence of TTX. Thus, we believe it was due to increased GABA release due to carbachol excitation of local GABAergic neurons, which in addition to causing fast GABA A receptor-mediated IPSCs, acts on GABA B receptors on DRN neurons to cause a slow outward current (Kohlmeier et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse

Yang

Brown

2014

Neuroscience

View full text Add to dashboard Cite

Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative serotonin neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods leads to excitation of 5-HT neurons via activation of nicotinic receptors located postsynaptically and presynaptically on excitatory afferents.

show abstract

“…This finding suggests that the outward current was indeed a potassium current that could have been activated through a G protein-related mechanism. G proteins are known to interact both with cation channels [327] and chloride channels [328][329][330][331][332] that can produce sustained outward currents. One family of G proteinassociated channels that is thought to have broad relevance in the CNS is that of the G protein-coupled inwardly-rectifying potassium channels (GIRKs) [333,334].…”

Section: Effects Of Nicotine In the Presence Of Intracellular Antagonmentioning

confidence: 99%

Mechanistic bases for the adverse interaction of nicotine and chronic pain

Jareczek¹

View full text Add to dashboard Cite

γ-Hydroxybutyric acid induces actions via the GABAB receptor in arousal and motor control-related nuclei: Implications for therapeutic actions in behavioral state disorders

Cited by 20 publications

References 67 publications

Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine

Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine

The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse

Mechanistic bases for the adverse interaction of nicotine and chronic pain

Contact Info

Product

Resources

About