Activation of serotonin-3 receptors increases dopamine release within the ventral tegmental area of Wistar and alcohol-preferring (P) rats

Li, Wen; Thielen, Richard J.; Rodd, Zachary A.; McBride, William J.

doi:10.1016/j.alcohol.2007.01.001

Cited by 40 publications

(35 citation statements)

References 31 publications

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“…Indeed, 5-HT 3 binding was detected in the rat VTA using [ 3 H]quipazine (Perry, 1990), whereas studies using more selective ligands with a higher affinity than quipazine did not identify the presence of 5-HT 3 -binding sites in the rat VTA (Barnes et al, 1990 ;Hamon, 1992 ;Laporte et al, 1992). Nonetheless, local perfusion of the 5-HT 3 receptor agonist m-chlorophenyl-biguanide in the VTA, via a microdialysis probe, induces a dosedependent increase in extracellular level of DA (Campbell et al, 1996 ;Liu et al, 2006). Therefore very scarce 5-HT 3 receptors possibly present in the VTA might still be functionally important.…”

Section: Discussionmentioning

confidence: 90%

Long-term administration of monoamine oxidase inhibitors alters the firing rate and pattern of dopamine neurons in the ventral tegmental area

Chenu

Mansari

Blier

2008

Int. J. Neuropsychopharm.

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Monoamine oxidase inhibitors (MAOIs) exert their antidepressant action by increasing the function of the serotonin (5-HT), norepinephrine and dopamine (DA) systems. There is, however, limited electrophysiological data on the effects of MAOIs on DA neurons. The effects of 2-d and 21-d administration of three MAOIs were investigated (clorgyline, selective MAOI-A; deprenyl, selective MAOI-B; phenelzine, non-selective MAOI) on the firing activity of DA neurons in the ventral tegmental area using in-vivo electrophysiology in rats. Short-term clorgyline (1 mg/kg) and phenelzine (2.5 mg/kg) was devoid of effect on DA neurons, whereas prolonged administration significantly decreased their firing rate (by 30% and 20%, respectively), number of bursts (by 80% and 45%, respectively), and percentage of spikes occurring in bursts only in clorgyline-treated rats (70%). Deprenyl (0.25 mg/kg) was without effects. DA firing was restored in clorgyline-treated rats by inhibiting 5-HT synthesis using para-chlorophenylalanine (p-CPA; 300 mg/kg. d for three consecutive days). The 5-HT3 antagonist ondansetron (0.5 mg/kg) was devoid of effect in control rats, but completely reversed the alterations of DA neuronal activity in clorgyline-treated rats. An attenuation of DA neuronal activity was thus produced by prolonged blockade of MAOA activity. The absence of effect of MAOA inhibition after subacute administration suggested an indirect mechanism. This was confirmed by the observation that p-CPA antagonized the effects of clorgyline. Since ondansetron completely reversed the effects of clorgyline on DA neuronal activity, the effects of MAOA inhibition appeared to be mediated by 5-HT3 receptors.

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Section: Discussionmentioning

confidence: 90%

Long-term administration of monoamine oxidase inhibitors alters the firing rate and pattern of dopamine neurons in the ventral tegmental area

Chenu

Mansari

Blier

2008

Int. J. Neuropsychopharm.

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“…Although the cellular localization of these receptors remains unknown, activation of 5-HT 3 receptors in the posterior VTA produces a stimulatory net effect on local dopamine neurons (Liu et al, 2006). A previous electrophysiological study indicated that EtOH at doses of 1 to 25 mM (approximately 5-110 mg%) induced a 5 to 20% increase of 5-HT 3 receptor-mediated ion currents in vitro (Lovinger and White, 1991).…”

Section: Icsa Of Etoh Andmentioning

confidence: 99%

Synergistic Self-Administration of Ethanol and Cocaine Directly into the Posterior Ventral Tegmental Area: Involvement of Serotonin-3 Receptors

Ding¹,

Oster²,

Hauser³

et al. 2011

J Pharmacol Exp Ther

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Ethanol (EtOH) and cocaine are both self-administered into the posterior ventral tegmental area (VTA). Self-administration of either drug is prevented by coadministration of a serotonin (5-HT 3 ) receptor antagonist. Electrophysiological studies indicated that cocaine and EtOH can act synergistically to stimulate VTA dopamine neurons. The current experiment assessed whether cocaine and EtOH would synergistically interact to produce a reinforcing action within the posterior VTA. Adult female Wistar rats were randomly assigned to one of 13 groups. There were three control groups: artificial cerebrospinal fluid (aCSF), a subthreshold EtOH (100 mg%) group, and a subthreshold cocaine (25 pmol/100 nl) group. The other groups self-administered 50 or 75 mg% EtOH containing 6.25, 12.5, or 25 pmol/100 nl cocaine or 100 mg% EtOH containing 3.12, 6.25, 12.5, or 25 pmol/100 nl cocaine. All rats received the assigned infusate for sessions 1 through 4, aCSF alone in sessions 5 and 6, and the original infusate during session 7. The effects of adding a 5-HT 3 receptor antagonist [tropisetron, C 17 pmol/100 nl) were determined. Rats failed to self-administer aCSF or the subthreshold concentration of EtOH or cocaine. All three concentrations of EtOH (50, 75, and 100 mg%) combined with cocaine (12.5 and 25 pmol/100 nl) supported self-administration. Adding a 5HT 3 receptor antagonist attenuated coadministration of EtOH ϩ cocaine. Overall, the data indicate that the reinforcing properties of EtOH and cocaine interacted synergistically within the posterior VTA, and these synergistic effects were mediated, at least in part, by activation of local 5-HT 3 receptors.

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“…The DRN has projections into numerous brain regions, including the mesolimbic regions important in reward and addiction (amygdala, hippocampus, caudate putamen, substantia nigra and ventral tegmental area). Projections from the raphe nuclei mediate dopamine release in the ventral tegmental area (Liu et al, 2006b; Rodd et al, 2007; Sari et al, 2011). Ethanol-naïve P rats have fewer serotonergic neurons in the DRN than ethanol-naïve NP rats and decreased serotonergic projections into terminal regions (Zhou et al, 1994).…”

Section: Introduction/backgroundmentioning

confidence: 99%

Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking

McClintick

McBride

Bell

et al. 2015

Pharmacology Biochemistry and Behavior

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Alcohol binge-drinking during adolescence is a serious public health concern with long-term consequences. We used RNA sequencing to assess the effects of excessive adolescent ethanol binge-drinking on gene expression in the dorsal raphe nucleus (DRN) of alcohol preferring (P) rats. Repeated binges across adolescence (three 1h sessions across the dark-cycle per day, 5 days per week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5 – 3 g/kg/session) significantly altered the expression of approximately one-third of the detected genes. Multiple neurotransmitter systems were altered, with the largest changes in the serotonin system (21 of 23 serotonin-related genes showed decreased expression) and GABA-A receptors (8 decreased and 2 increased). Multiple neuropeptide systems were also altered, with changes in the neuropeptide Y and corticotropin-releasing hormone systems similar to those associated with increased drinking and decreased resistance to stress. There was increased expression of 21 of 32 genes for potassium channels. Expression of downstream targets of CREB signaling was increased. There were also changes in expression of genes involved in inflammatory processes, axonal guidance, growth factors, transcription factors, and several intracellular signaling pathways. These widespread changes indicate that excessive binge drinking during adolescence alters the functioning of the DRN and likely its modulation of many regions of the central nervous system, including the mesocorticolimbic system.

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Activation of serotonin-3 receptors increases dopamine release within the ventral tegmental area of Wistar and alcohol-preferring (P) rats

Cited by 40 publications

References 31 publications

Long-term administration of monoamine oxidase inhibitors alters the firing rate and pattern of dopamine neurons in the ventral tegmental area

Long-term administration of monoamine oxidase inhibitors alters the firing rate and pattern of dopamine neurons in the ventral tegmental area

Synergistic Self-Administration of Ethanol and Cocaine Directly into the Posterior Ventral Tegmental Area: Involvement of Serotonin-3 Receptors

Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking

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