Clomipramine Enhances the Excitatory Actions of Dorsal Raphe Nucleus Stimulation in Lateral Septal Neurons in the Rat

Contreras, Carlos M.; Ml, Marván; Ramírez-Morales, A. O.; Muñoz-Méndez, A

doi:10.1159/000118959

Cited by 15 publications

(3 citation statements)

References 23 publications

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“…Several antidepressants produce an increase in firing rate [20, 44], which agrees with the present results. Such antidepressants exert their main actions on the serotonergic system [45], and we detected opposite actions between fluoxetine and diazepam, AF, and the FAT mixture, suggesting minimal participation of 5-HT in the effects of AF and its FATs.…”

Section: Discussionsupporting

confidence: 92%

Amniotic Fluid or Its Fatty Acids Produce Actions Similar to Diazepam on Lateral Septal Neurons Firing Rate

Gutiérrez-García

Contreras

Vásquez-Hernández

2013

The Scientific World Journal

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Human amniotic fluid (AF) contains eight fatty acids (FATs), and both produce anxiolytic-like effects in adult rats and appetitive responses in human newborns. The medial amygdala and lateral septal nucleus function are related to social behavior, but the action of AF or its FATs in this circuit is known. We obtained 267 single-unit extracellular recordings in Wistar rats treated with vehicle (1 mL, s.c.; n = 12), human AF (1 mL, s.c.; n = 12), a FAT mixture (1 mL, s.c.; n = 13), diazepam (1 mg/kg, i.p.; n = 11), and fluoxetine (1 mg/kg, p.o.; n = 12). Compared with the vehicle group, the spontaneous septal firing rate in the AF, FAT mixture, and diazepam groups was the lowest and in the fluoxetine group the highest. Cumulative peristimulus histograms indicated that the significant change in septal firing occurred only in the AF and FAT mixture groups and exclusively in those neurons that increased their firing rate during amygdala stimulation. We conclude that human AF and its FATs produce actions comparable to anxiolytic drugs and are able to modify the responsivity of a circuit involved in social behavior, suggesting facilitation of social recognition processes by maternal-fetal fluids.

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Section: Discussionsupporting

confidence: 92%

Amniotic Fluid or Its Fatty Acids Produce Actions Similar to Diazepam on Lateral Septal Neurons Firing Rate

Gutiérrez-García

Contreras

Vásquez-Hernández

2013

The Scientific World Journal

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“…The LSN is also densely innervated by serotonergic afferents from the dorsal raphe nucleus ( Köhler et al, 1982 ; Risold and Swanson, 1997 ) and expresses numerous 5-HT receptor subtypes (e.g., 5-HT1-4 and 5-HT7) at moderate to high levels ( Biegon et al, 1982 ; Pazos and Palacios, 1985 ; Pazos et al, 1985 ; du Jardin et al, 2014 ). Electrical stimulation of the raphe has been shown to increase the activity of LSN neurons, an effect that is potentiated by antidepressants ( Contreras et al, 1989 , 1993 , 2001 ; Sheehan et al, 2004 ). Bath applied 5-HT has complex effects on the membrane activity of septal neurons, but may increase their responsiveness to excitatory drive by suppressing action potential afterhyperpolarization, facilitating the afterdepolarization, and decreasing inhibitory IPSPs ( Joëls et al, 1986 ; Joëls and Gallagher, 1988 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of Vortioxetine on Synaptic Integration in Prefrontal-Subcortical Circuits: Comparisons with Escitalopram

et al. 2017

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Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT) transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC), however, the impact of this compound on related prefrontal-subcortical circuits is less clear. Thus, the current study examined the impact of systemic vortioxetine administration (0.8 mg/kg, i.v.) on spontaneous spiking and spikes evoked by electrical stimulation of the mPFC in the anterior cingulate cortex (ACC), medial shell of the nucleus accumbens (msNAc), and lateral septal nucleus (LSN) in urethane-anesthetized rats. We also examined whether vortioxetine modulated afferent drive in the msNAc from hippocampal fimbria (HF) inputs. Similar studies were performed using the selective 5-HT reuptake inhibitor [selective serotonin reuptake inhibitors (SSRI)] escitalopram (1.6 mg/kg, i.v.) to enable comparisons between the multimodal actions of vortioxetine and SSRI-mediated effects. No significant differences in spontaneous activity were observed in the ACC, msNAc, and LSN across treatment groups. No significant impact of treatment on mPFC-evoked responses was observed in the ACC. In contrast, vortioxetine decreased mPFC-evoked activity recorded in the msNAc as compared to parallel studies in control and escitalopram treated groups. Thus, vortioxetine may reduce mPFC-msNAc afferent drive via a mechanism that, in addition to an SSRI-like effect, requires 5-HT receptor modulation. Recordings in the LSN revealed a significant increase in mPFC-evoked activity following escitalopram administration as compared to control and vortioxetine treated groups, indicating that complex modulation of 5-HT receptors by vortioxetine may offset SSRI-like effects in this region. Lastly, neurons in the msNAc were more responsive to stimulation of the HF following both vortioxetine and escitalopram administration, indicating that elevation of 5-HT tone and 5-HT receptor modulation may facilitate excitatory hippocampal synaptic drive in this region. The above findings point to complex 5-HT receptor-dependent effects of vortioxetine which may contribute to its unique impact on the function of prefrontal-subcortical circuits and the development of novel strategies for treating mood disorders.

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“…LS hypotrophy is involved in depression, and neuronal density in the LS tends to decrease with MDD progression [ 58 ]. Animal studies have shown that antidepressant drugs can increase LS neural activity [ 59 , 60 , 61 , 62 ]. A recent study shows that LS GABAergic (LS GABA ) neurons regulate depression-related behaviors through their projections to the periaqueductal gray [ 63 ].…”

Section: Introductionmentioning

confidence: 99%

Activation of Somatostatin-Expressing Neurons in the Lateral Septum Improves Stress-Induced Depressive-like Behaviors in Mice

Sung

Lau

2022

Pharmaceutics

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Depression is a debilitating mood disorder with highly heterogeneous pathogenesis. The limbic system is well-linked to depression. As an important node in the limbic system, the lateral septum (LS) can modulate multiple affective and motivational behaviors. However, the role of LS in depression remains unclear. By using c-Fos expression mapping, we first screened and showed activation of the LS in various depression-related behavioral tests, including the forced swim test (FST), tail suspension test (TST), and sucrose preference test. In the LS, more than 10% of the activated neurons were somatostatin-expressing (SST) neurons. We next developed a microendoscopic calcium imaging method in freely moving mice and revealed that LSSST neural activity increased during mobility in the TST but not open field test. We hypothesize that LSSST neuronal activity is linked to stress and depression. In two mouse models of depression, repeated lipopolysaccharide (LPS) injection and chronic restraint stress (CRS), we showed that LS neuronal activation was suppressed. To examine whether the re-activation of LSSST neurons can be therapeutically beneficial, we optogenetically activated LSSST neurons and produced antidepressant-like effects in LPS-injected mice by increasing TST motility. Moreover, chemogenetic activation of LSSST neurons increased FST struggling in the CRS-exposed mice. Together, these results provide the first evidence of a role for LSSST neurons in regulating depressive-like behaviors in mice and identify them as a potential therapeutic target for neuromodulation-based intervention in depression.

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Clomipramine Enhances the Excitatory Actions of Dorsal Raphe Nucleus Stimulation in Lateral Septal Neurons in the Rat

Cited by 15 publications

References 23 publications

Amniotic Fluid or Its Fatty Acids Produce Actions Similar to Diazepam on Lateral Septal Neurons Firing Rate

Amniotic Fluid or Its Fatty Acids Produce Actions Similar to Diazepam on Lateral Septal Neurons Firing Rate

Impact of Vortioxetine on Synaptic Integration in Prefrontal-Subcortical Circuits: Comparisons with Escitalopram

Activation of Somatostatin-Expressing Neurons in the Lateral Septum Improves Stress-Induced Depressive-like Behaviors in Mice

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