Serotonin–GABA interactions modulate MDMA‐induced mesolimbic dopamine release

Bankson, Michael G.; Yamamoto, Bryan K.

doi:10.1111/j.1471-4159.2004.02763.x

Cited by 77 publications

(58 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 98%

“…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%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…As discussed for the nigrostriatal system, these effects may be mediated by actions on GABA cells in the VTA. Intra-VTA administration of the 5-HT2C inverse agonist SB 206553 has been shown both to attenuate MDMA-induced increases in VTA GABA and potentiate the concurrent increase in NA DA (Bankson and Yamamoto, 2004). Likewise, systemic administration of a 5-HT2C agonist has been shown to excite all non-DA, presumably GABAergic cells in the VTA, suggesting that 5-HT2C receptors in this region are localized to GABAergic neurons (Di Giovanni et al, 2001).…”

Section: Mesolimbic Pathwaymentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

525

311

View full text Add to dashboard Cite

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.

show abstract

“…Several investigators have demonstrated that MDMA produces a marked increase in the extracelllular concentration of DA in the n. accumbens (Cadoni et al, 2005;Kankaanpaa et al, 1998;Marona-Lweicka et al, 1996;Amato et al, 2007;O-Shea et al, 2005;Bankson and Yamamoto, 2004). As in the striatum, MDMA-induced DA release in the n. accumbens appears also to be modulated by 5-HT-GABA interactions.…”

Section: Nucleusmentioning

confidence: 99%

“…As noted above, MDMA-induced suppression of nigral GABA release following 5-HT2A/2C receptor activation disinhibits striatal DA release. However, an MDMA-induced increase in GABA release within the ventral tegmental area (VTA), subsequent to 5-HT2B/C receptor activation, appears to limit the magnitude of MDMAinduced DA release in the n. accumbens (Bankson and Yamamoto, 2004).…”

Section: Nucleusmentioning

confidence: 99%

Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons

Gudelsky

Yamamoto

2008

Pharmacology Biochemistry and Behavior

Self Cite

120

View full text Add to dashboard Cite

Abstract3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative and a popular drug of abuse that exhibits mild hallucinogenic and rewarding properties and engenders feelings of connectedness and openness. The unique psychopharmacological profile of this drug of abuse most likely is derived from the property of MDMA to promote the release of dopamine and serotonin (5-HT) in multiple brain regions. The present review highlights primarily data from studies employing in vivo microdialysis that detail the actions of MDMA on the release of these neurotransmitters. Data from in vivo microdialysis experiments indicate that MDMA, like most amphetamine derivatives, increases the release of dopamine in the striatum, n. accumbens and prefrontal cortex. However, the release of dopamine evoked by MDMA in each of these brain regions appears to be modulated by concomitantly released 5-HT and the subsequent activation of 5-HT2A/C or 5-HT2B/C receptors. In addition to its stimulatory effect on the release of monoamines, MDMA also enhances the release of acetylcholine in the striatum, hippocampus and prefrontal cortex, and this cholinergic response appears to be secondary to the activation of histaminergic, dopaminergic and/or serotonergic receptors. Beyond the acute stimulatory effect of MDMA on neurotransmitter release, MDMA also increases the extracellular concentration of energy substrates, e.g., glucose and lactate in the brain. In contrast to the acute stimulatory actions of MDMA on the release of monoamines and acetylcholine, the repeated administration of high doses of MDMA is thought to result in a selective neurotoxicity to 5-HT axon terminals in the rat. Additional studies are reviewed that focus on the alterations in neurotransmitter responses to pharmacological and physiological stimuli that accompany MDMA-induced 5-HT neurotoxicity.

show abstract

Serotonin–GABA interactions modulate MDMA‐induced mesolimbic dopamine release

Cited by 77 publications

References 49 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

Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons

Contact Info

Product

Resources

About