scholarly journals Neural Circuit in the Dorsal Raphe Nucleus Responsible for Cannabinoid-Mediated Increases in 5-HT Efflux in the Nucleus Accumbens of the Rat Brain

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Rui Tao ◽  
Zhiyuan Ma

In vivo microdialysis was used in this study to reveal the role of cannabinoids in regulating serotonin (5-HT) efflux in the nucleus accumbens (NAcc) and dorsal raphe nucleus (DRN). The cannabinoid CB1 receptor agonists WIN55212-2 and CP55940 systematically administered to rats caused significant increases in 5-HT efflux in the NAcc but failed to have an effect in the DRN. To reveal mechanisms underlying regionally selective responses, we tested the hypothesis that cannabinoids have both direct and indirect effects on 5-HT efflux, depending on the location of CB1 receptors in the neural circuit between DRN and NAcc. We showed that the direct effect of cannabinoids caused a reduction in 5-HT efflux whereas the indirect effect resulted in an increase. Furthermore, the indirect effect was blocked by the GABAA receptor antagonist bicuculline in the DRN, suggesting that the action is likely due to a presynaptic inhibition on GABAergic activity that exerts a tonic influence on neuronal circuits regulating 5-HT efflux. Involvement of GABAergic neurons was confirmed by measuring changes in GABA efflux. Taken together, our study suggests that cannabinoids may have direct and indirect effects on the 5-HT regulatory circuits, resulting in regionally selective changes of 5-HT efflux in the brain.






2004 ◽  
Vol 182 (1) ◽  
pp. 11-21 ◽  
Author(s):  
M Robichaud ◽  
G Debonnel

Important gender differences in mood disorders result in a greater susceptibility for women. Accumulating evidence suggests a reciprocal modulation between the 5-hydroxytryptamine (5-HT) system and neuroactive steroids. Previous data from our laboratory have shown that during pregnancy, the firing activity of 5-HT neurons increases in parallel with progesterone levels. This study was undertaken to evaluate the putative modulation of the 5-HT neuronal firing activity by different neurosteroids. Female rats received i.c.v. for 7 days a dose of 50 micro g/kg per day of one of the following steroids: progesterone, pregnenolone, 5beta-pregnane-3,20-dione (5beta-DHP), 5beta-pregnan-3alpha-ol,20-one, 5beta-pregnan-3beta-ol,20-one, 5alpha-pregnane-3,20-dione, 5alpha-pregnan-3alpha-ol,20-one (allopregnanolone, 3alpha,5alpha-THP), 5alpha-pregnane-3beta-ol,20-one and dehydroepiandrosterone (DHEA). 5beta-DHP and DHEA were also administered for 14 and 21 days (50 micro g/kg per day, i.c.v.) as well as concomitantly with the selective sigma 1 (sigma1) receptor antagonist NE-100. In vivo, extracellular unitary recording of 5-HT neurons performed in the dorsal raphe nucleus of these rats revealed that DHEA, 5beta-DHP and 3alpha,5alpha-THP significantly increased the firing activity of the 5-HT neurons. Interestingly, 5beta-DHP and DHEA showed different time-frames for their effects with 5beta-DHP having its greatest effect after 7 days to return to control values after 21 days, whereas DHEA demonstrated a sustained effect over the 21 day period. NE-100 prevented the effect of DHEA but not of 5beta-DHP, thus indicating that its sigma1 receptors mediate the effect of DHEA but not that of 5beta-DHP. In conclusion, our results offer a cellular basis for potential antidepressant effects of neurosteroids, which may prove important particularly for women with affective disorders.



2019 ◽  
Vol 1719 ◽  
pp. 243-252 ◽  
Author(s):  
Naoya Nishitani ◽  
Yu Ohmura ◽  
Kazuki Nagayasu ◽  
Norihiro Shibui ◽  
Shuji Kaneko ◽  
...  


1996 ◽  
Vol 737 (1-2) ◽  
pp. 308-312 ◽  
Author(s):  
Mihály Hajós ◽  
Trevor Sharp ◽  
Nigel R Newberry


2002 ◽  
Vol 80 (12) ◽  
pp. 1158-1166 ◽  
Author(s):  
Yoko Hagino ◽  
Masayuki Watanabe

In vivo microdialysis in conscious rats was used to examine the effect of clozapine on serotonin (5-hydroxy tryptamine, 5-HT) efflux in the prefrontal cortex and dorsal raphe nucleus and dopamine efflux in the prefrontal cortex. Both systemic and local administration of clozapine (systemic,10 or 20 mg/kg, i.p.; local, 100 μM) increased 5-HT efflux in the dorsal raphe. However, in the prefrontal cortex, dialysate 5-HT increased when clozapine (100 μM) was administered through the probe, while no effect was observed when it was administered systemically. By pretreatment with the selective 5-HT1A receptor antagonist p-MPPI (3 mg/kg, i.p.), systemic treatment of clozapine (10 mg/kg, i.p.) significantly increased 5-HT efflux in the prefrontal cortex. This result suggests that the ability of clozapine to enhance the extracellular concentrations of 5-HT in the dorsal raphe attenuates this drug's effect in the frontal cortex, probably through the stimulation of 5-HT1A somatodendritic autoreceptors in the dorsal raphe. We also found that pretreatment with p-MPPI (3 mg/kg, i.p.) attenuated by 45% the rise in cortical dopamine levels induced by clozapine (10 mg/kg, i.p.). These findings imply that the reduction in serotonergic input from the dorsal raphe nucleus induced by clozapine could lead to an increase in dopamine release in the prefrontal cortex. Key words: 5-HT1A receptor, clozapine, microdialysis, 5-HT, dopamine.



2003 ◽  
Vol 88 (6) ◽  
pp. 1373-1379 ◽  
Author(s):  
Analía Bortolozzi ◽  
Mercè Amargós-Bosch ◽  
Miklos Toth ◽  
Francesc Artigas ◽  
Albert Adell


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Laifu Li ◽  
Li-Zi Zhang ◽  
Zhi-Xiong He ◽  
Huan Ma ◽  
Yu-Ting Zhang ◽  
...  

Consolation is a common response to the distress of others in humans and some social animals, but the neural mechanisms underlying this behavior are not well characterized. By using socially monogamous mandarin voles, we found that optogenetic or chemogenetic inhibition of 5-HTergic neurons in the dorsal raphe nucleus (DR) or optogenetic inhibition of 5-HT terminals in the anterior cingulate cortex (ACC) significantly decreased allogrooming time in the consolation test and reduced sociability in the three-chamber test. The release of 5-HT within the ACC and the activity of DR neurons were significantly increased during allogrooming, sniffing and social approaching. Finally, we found that the activation of 5-HT1A receptors in the ACC was sufficient to reverse consolation and sociability deficits induced by the chemogenetic inhibition of 5-HTergic neurons in the DR. Our study provided first direct evidence that DR-ACC 5-HTergic neural circuit is implicated in consolation-like behaviors and sociability.



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