Involvement of 5-HT1B receptors within the ventral tegmental area in regulation of mesolimbic dopaminergic neuronal activity via GABA mechanisms: a study with dual-probe microdialysis

Yan, Qing‐Shan; Zheng, Shizhong; Yan, Shu-E

doi:10.1016/j.brainres.2004.06.053

Cited by 69 publications

(53 citation statements)

References 63 publications

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“…Therefore, the elevated levels of mRNA for the GABA A d-subunit in the VTA of FSL rats might be due to an intrinsic GABA-ergic intraneuron modulation (compensation) for low levels of DHEA in this brain region (Concas et al, 1999;Gulinello et al, 2001;Holt et al, 1996;Mahmoudi et al, 1997). The contrasting lower levels of mRNA for the d-subunit in the NAc of FSL compared to SD rats can be explained by different localization of GABA modulation on ascending neurons (Akiyama et al, 2004;Bankson and Yamamoto, 2004;Tao and Auerbach, 2002;Yan et al, 2004). Our results may point to a different role for the GABA A Rs in the NAc compared to the VTA, some of which may be explained by localization of the receptors pre-or post-synaptically (Ikemoto et al, 1997;Yan et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The contrasting lower levels of mRNA for the d-subunit in the NAc of FSL compared to SD rats can be explained by different localization of GABA modulation on ascending neurons (Akiyama et al, 2004;Bankson and Yamamoto, 2004;Tao and Auerbach, 2002;Yan et al, 2004). Our results may point to a different role for the GABA A Rs in the NAc compared to the VTA, some of which may be explained by localization of the receptors pre-or post-synaptically (Ikemoto et al, 1997;Yan et al, 2004). Moreover, our results suggest that an imbalance in the mesolimbic GABA-ergic system together with the alterations in DHEA levels may lead to the pathological behavioral outcomes observed in the FSL rats.…”

Section: Discussionmentioning

confidence: 99%

“…The GABA-ergic system is an important regulator of dopaminergic neurons (Akiyama et al, 2004), which are relevant to depression (Dremencov et al, 2006;Friedman et al, 2007). Specifically, GABA A Rs within the VTA regulate dopamine output to the NAc (Bankson and Yamamoto, 2004;Yan et al, 2004), suggesting a modulatory role for these receptors in depression (Garcia-Alloza et al, 2006). Furthermore, co-administration of a GABA A agonist (muscimol) and DHEA blocked the beneficial effect of DHEA on depressive behavior (Figure 4), confirming that the GABA A R is the main target for DHEA in depression.…”

Section: Discussionmentioning

confidence: 99%

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DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

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Alterations in the levels of dehydroepiandrosterone (DHEA) in the brain can allosterically modulate g-aminobutyric-acid-type-A (GABA A R), N-methyl-D-aspartate (NMDAR), and Sigma-1 (s1R) receptors. In humans, DHEA has antidepressive effects; however, the mechanism is unknown. We examined whether alterations in DHEA also occur in an animal model of depression, the Flinders-sensitiveline (FSL) rats, with the intention of determining the brain site of DHEA action and its antidepressant mechanism. We discovered that DHEA levels were lower in some brain regions involved with depression of FSL rats compared to Sprague-Dawley (SD) controls. Moreover, DHEA (1 mg/kg IP for 14 days)-treated FSL rats were more mobile in the forced swim test than FSL controls. In the NAc and VTA, significant changes were observed in the levels of the d-subunit of GABA A , but not of s1R mRNA, in FSL rats compared to SD rats. The d-subunit controls the sensitivity of the GABA A R to the neurosteroid. Indeed, treatment (14 days) of FSL rats with the GABA A agonist muscimol (0.5 mg/kg), together with DHEA (a negative modulator of GABA A ), reversed the effect of DHEA on immobility in the swim test. Perfusion of DHEA sulfate (DHEAS) (3 nM and 30 nM for 14 days) into the VTA and NAc of FSL rats improved their performance in the swim test for at least 3 weeks post-treatment. Our results imply that alterations in DHEA are involved in the pathophysiology of depression and that the antidepressant action of DHEA is mediated via GABA A Rs in the NAc and VTA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

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“…Administration of the 5-HT1B receptor agonist CP 93129 into the VTA has been shown to increase DA levels in the NA (Yan and Yan, 2001a;O'Dell and Parsons, 2004;Yan et al, 2004) and concurrently decrease GABA in the VTA (O'Dell and Parsons, 2004;Yan et al, 2004). Systemic 5-HT1B agonism also decreases VTA GABA (Parsons et al, 1999).…”

Section: Mesolimbic Pathwaymentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

527

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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“…In terms of this interaction, it is of interest to note that 5-HT 1B (Yan and Yan, 2001;Yan et al, 2004) and 5-HT 2A Table 1. The motor activity was automatically quantified and cumulated for 60 min following MAP challenge (0.24 mg/kg, s.c.) on days 29 and 13 of withdrawal of the repeated treatment with MAP (PT 1; pretreatment 1) and that with PRX (PT 2; pretreatment 2), respectively.…”

Section: Discussionmentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitors, Fluoxetine and Paroxetine, Attenuate the Expression of the Established Behavioral Sensitization Induced by Methamphetamine

Kaneko

Kashiwa

Ito

et al. 2006

Neuropsychopharmacol

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To obtain an insight into the development of a new pharmacotherapy that prevents the treatment-resistant relapse of psychostimulantinduced psychosis and schizophrenia, we have investigated in the mouse the effects of selective serotonin reuptake inhibitors (SSRI), fluoxetine (FLX) and paroxetine (PRX), on the established sensitization induced by methamphetamine (MAP), a model of the relapse of these psychoses, because the modifications of the brain serotonergic transmission have been reported to antagonize the sensitization phenomenon. In agreement with previous reports, repeated MAP treatment (1.0 mg/kg a day, subcutaneously (s.c.)) for 10 days induced a long-lasting enhancement of the increasing effects of a challenge dose of MAP (0.24 mg/kg, s.c.) on motor activity on day 12 or 29 of withdrawal. The daily injection of FLX (10 mg/kg, s.c.) or PRX (8 mg/kg, s.c.) from 12 to 16 days of withdrawal of repeated MAP administration markedly attenuated the ability of the MAP pretreatment to augment the motor responses to the challenge dose of the stimulant 13 days after the SSRI injection. The repeated treatment with FLX or PRX alone failed to affect the motor stimulation following the challenge of saline and MAP 13 days later. These results suggest that the intermittent and repetitive elevation of serotonergic tone may inhibit the expression of the motor sensitization induced by pretreatment with MAP. It is proposed that clinically available serotonin reuptake inhibitors could be useful for preventing the recurrence of hallucinatory-paranoid state in drug-induced psychosis and schizophrenia.

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Involvement of 5-HT1B receptors within the ventral tegmental area in regulation of mesolimbic dopaminergic neuronal activity via GABA mechanisms: a study with dual-probe microdialysis

Cited by 69 publications

References 63 publications

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Selective Serotonin Reuptake Inhibitors, Fluoxetine and Paroxetine, Attenuate the Expression of the Established Behavioral Sensitization Induced by Methamphetamine

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