Non-competitive antagonists are potent activators of ventral tegmental A10 dopamine neurons

French, Edward D.; Ceci, Angelo

doi:10.1016/0304-3940(90)90823-r

Cited by 152 publications

(72 citation statements)

References 12 publications

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“…Overall, these findings suggest that measures of dopamine neurotransmission might enable detection of rapidly acting antidepressant drugs and, in addition, that mGlu2/3 receptor antagonists might be antidepressant in patients. We demonstrate here that the NMDA receptor antagonist ketamine, which has shown rapid, robust, and sustained antidepressant efficacy in treatment-resistant depressed (TRD) patients (reviewed in Abdallah et al, 2015), potently modulates mesolimbic dopamine transmission, as demonstrated by an increase in spontaneously active dopamine cells in the VTA (see also French and Ceci, 1990), increased dopamine release in the nucleus accumbens and prefrontal cortex, and potentiated quinpirole-stimulated locomotor behavior. Consistent with the growing experimental literature on parallel mechanisms in the pharmacological actions of ketamine and mGlu2/3 receptor antagonists (Alt et al, 2006;Li et al, 2010, Dwyer et al, 2012, we show here that commonalties exist at the level of dopamine neurotransmission as well…”

Section: Rapidly Acting Antidepressant Actions Of Ly341495 Discussionmentioning

confidence: 93%

The Rapidly Acting Antidepressant Ketamine and the mGlu2/3 Receptor Antagonist LY341495 Rapidly Engage Dopaminergic Mood Circuits

Witkin

Monn

Schoepp

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Ketamine is a rapidly acting antidepressant in patients with treatment-resistant depression (TRD). Although the mechanisms underlying these effects are not fully established, inquiry to date has focused on the triggering of synaptogenesis transduction pathways via glutamatergic mechanisms. Preclinical data suggest that blockade of metabotropic glutamate (mGlu2/3) receptors shares many overlapping features and mechanisms with ketamine and may also provide rapid efficacy for TRD patients. Central dopamine circuitry is recognized as an end target for mood regulation and hedonic valuation and yet has been largely neglected in mechanistic studies of antidepressant-relevant effects of ketamine. Herein, we evaluated the changes in dopaminergic neurotransmission after acute administration of ketamine and the mGlu2/3 receptor antagonist LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid ] in preclinical models using electrophysiologic, neurochemical, and behavioral endpoints. When given acutely, both ketamine and LY341495, but not the selective serotonin reuptake inhibitor (SSRI) citalopram, increased the number of spontaneously active dopamine neurons in the ventral tegmental area (VTA), increased extracellular levels of dopamine in the nucleus accumbens and prefrontal cortex, and enhanced the locomotor stimulatory effects of the dopamine D 2/3 receptor agonist quinpirole. Further, both ketamine and LY341495 reduced immobility time in the tail-suspension assay in CD1 mice, which are relatively resistant to SSRI antidepressants. Both the VTA neuronal activation and the antidepressant phenotype induced by ketamine and LY341495 were attenuated by the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-(9CI)-benzo[f]quinoxaline-7-sulfonamide, indicating AMPA-dependent effects. These findings provide another overlapping mechanism of action of ketamine and mGlu2/3 receptor antagonism that differentiates them from conventional antidepressants and thus support the potential rapidly acting antidepressant actions of mGlu2/3 receptor antagonism in patients.

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Section: Rapidly Acting Antidepressant Actions Of Ly341495 Discussionmentioning

confidence: 93%

The Rapidly Acting Antidepressant Ketamine and the mGlu2/3 Receptor Antagonist LY341495 Rapidly Engage Dopaminergic Mood Circuits

Witkin

Monn

Schoepp

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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“…Electrophysiological studies have demonstrated sigma receptor agonist-induced increases in firing of ventral tegmental dopamine neurons (16) and decreases in firing of substantia nigral dopamine neurons (8,51,52). DTG, specifically, did not increase firing of ventral tegmental neurons (16), but decreased (52) or had no effect on (70) firing of substantia nigra neurons.…”

Section: Discussionmentioning

confidence: 99%

The Delayed Effects of DTG and MK-801 on Latent Inhibition in a Conditioned Taste-Aversion Paradigm

Turgeon¹,

Auerbach²,

Duncan-Smith³

et al. 2000

Pharmacology Biochemistry and Behavior

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. The delayed effects of DTG and MK-801 on latent inhibition in a conditioned taste-aversion paradigm. PHARMACOL BIOCHEM BEHAV 66 (3) 533-539, 2000.-The delayed effects of phencyclidine (PCP) have been shown to disrupt latent inhibition (LI) in a conditioned taste-aversion paradigm. In an attempt to understand the mechanism of this disruption, the delayed effects of the selective sigma receptor agonist 1,3-Di(2-tolyl)guanidine (DTG) and the selective NMDA receptor antagonist MK-801 on latent inhibition were assessed in the same paradigm. Water-deprived male rats were allowed access to either water (nonpreexposed; NPE) or 5% sucrose (preexposed; PE) for 30 min on 2 consecutive days. On the third day, animals were allowed access to sucrose and subsequently injected with lithium chloride. On the forth day, animals were allowed access to both sucrose and water. LI was assessed by comparing the percent sucrose consumed in PE and NPE groups on the fourth day. DTG (1.0, 5.0, or 10.0 mg/kg), MK-801 (0.5, 1.0, or 2.0 mg/kg), or vehicle was administered IP 20 h before preexposure (days 1 and 2) and conditioning (day 3). In vehicle-treated groups, PE animals consumed a significantly higher percent sucrose on the test day than NPE animals, indicating the presence of LI. DTG (10.0 mg/kg) and MK-801 (2.0 mg/kg) decreased the percent sucrose consumed by animals in the PE group to the level observed in the NPE group, indicating disrupted LI. However, this dose of MK-801 was found to produce a decrease in percent sucrose consumed in PE animals not treated with lithium chloride, indicating that the decrease observed in the LI paradigm could be due to MK-801-induced decrease in taste preference for sucrose rather than a disruption of LI. Lower doses of MK-801 that did not produce a decrease in taste preference for sucrose did not significantly disrupt LI. None of the doses of DTG tested altered taste preference for sucrose. These data suggest a role for sigma receptors in the previously observed PCP-induced disruption of LI. LATENT inhibition (LI) is the impaired acquisition of a conditioned response to a stimulus that has been previously presented without reinforcement (35). LI is thought to be a measure of an organism's capacity to ignore irrelevant stimuli, and has been demonstrated in a variety of species including humans (4,35,36). Disruption of LI has been observed in nonmedicated acute schizophrenics (4) as well as animals and humans treated with the psychotomimetic drug amphetamine (14,22,49,(64)(65)(66)(67). Medicated schizophrenic patients do not demonstrate disrupted LI (4,37). In addition, antipsychotic medications reverse amphetamine-induced disruption of LI in animals (49,68), and can enhance LI on their own (11,15). These observations suggest that the disruption of LI is a useful animal model for this specific attentional deficit seen in schizophrenia (12,15). Phencyclidine (PCP) is a drug that can produce a psychotomimetic effect in humans (3,28,38) as well as a number of behavioral and cognitive changes in animals...

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“…The PFC projection to the VTA would appear to have the opposite function; the mesolimbic dopamine system, activated by PFC stimulation, projects to and makes symmetric, presumably inhibitory, synaptic contact with NAS medium spiny neurons (Sesack and Pickel, 1992). Previous reports have shown that stimulation of glutamate receptors activates dopaminergic (Grenhoff et al, 1988a;Kalivas et al, 1989;French and Ceci, 1990;Suaud-Chagny et al, 1992;Chergui et al, 1993;Mercuri et al, 1993;Wang and French, 1993a,b) as well as nondopaminergic (Wang and French, 1995) neurons in the VTA. The present study does not identify the VTA targets of PFC input; electron microscopic evidence indicates that PFC projections make asymmetric, presumably excitatory, synapses on both dopaminergic and nondopaminergic neurons (Sesack and Pickel, 1992).…”

Section: Pfc Self-stimulation and Vta Glutamatementioning

confidence: 97%

“…The PFC fibers make asymmetric, presumably excitatory, monosynaptic contacts on dopaminergic and nondopaminergic VTA neurons (Sesack and Pickel, 1992). Excitatory amino acids are the primary neurotransmitters of cortical efferents (Spencer, 1976;McGeer et al, 1977;Fonnum et al, 1981;Hassler et al, 1982;Christie, 1985;Girault et al, 1986;Young and Bradford, 1986) (Grenhoff et al, 1988a;French and Ceci, 1990;Johnson et al, 1992; Suaud-Chagny et aI., 1992;Chergui et al, 1993;Mercuri et al, 1993;Wang and French, 1993a) and increases dopamine release in the nucleus accumbens septi (NAS) (Kalivas et al, 1989;Wang et al, 1994;Westerink et al, 1996). Electrical stimulation of the PFC increases the activity of dopaminergic VTA cells , induces burst firing (Gariano and Groves, 1988;Murase et al, 1993;Chergui et al, 1994; Tong et al, 1996a,b), and increases dopamine release in terminal fields including the NAS (Nieoullon et al, 1978;Murase et al, 1993; Fibiger, 1993, 1995;.…”

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confidence: 99%

Increase of Extracellular Glutamate and Expression of Fos‐Like Immunoreactivity in the Ventral Tegmental Area in Response to Electrical Stimulation of the Prefrontal Cortex

Rossetti¹,

Marcangione

Wise

1998

Journal of Neurochemistry

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Electrical stimulation of the medial prefrontal cortex caused glutamate release in the ventral tegmental area (VTA) of freely moving animals. Cathodal stimulation was given through monopolar electrodes in 0.1-ms pulses at an intensity of 300 biA and frequencies of 4-120 Hz. Glutamate was measured in 10-min perfusate samples by HPLC coupled with fluorescence detection following precolumn derivatization with o-phthaldialdehyde/ß-mercaptoethanol. The stimulation-induced glutamate release was frequency dependent and was blocked by the infusion of the sodium channel blocker tetrodotoxin (10 1iM) through the dialysis probe. The stimulation also induced bilateral Fos-like immunoreactivity in ventral tegmental neurons, with a significantly greater number of Fos-positive cells on the stimulated side. These findings add to a growing body of evidence suggesting that the medial prefrontal cortex regulates dopamine release in the nucleus accumbens via its projection to dopamine cell bodies in the VTA. Key Words: Prefrontal cortexVentral tegmental area-Glutamate-Fos-like immunoreactivity-Microdialysis-Electrical stimulation. J. Neurochem. 70, 1503-1512 (1998).There has been considerable recent interest in the possibility that glutamatergic fibers from the medial prefrontal cortex (PFC) to the striatum might presynaptically regulate striatal dopamine release (Giorguieff et al., 1977;Chesselet, 1984;Cheramy et al., 1986;Romo et al., 1986b;Abercrombie and Zigmond, 1990;Grace, 1993;Greenamyre, 1993). Glutamate infusion into the striatum elevates extracellular dopamine, but this effect is insensitive to the perfusion of the sodium channel blocker tetrodotoxin (TTX) (Giorguieff et al., 1977;Roberts and Sharif, 1978;Roberts and Anderson, 1979; Marien et al., 1983;Clow and Jhamandas, 1989;Lonart and Zigmond, 1991; but see Youngren et al., 1993). Disinhibition of prefrontal cortex by local interference with GABAergic transmission (Karremann and Moghaddam, 1996) or by GABA infusion into the medial thalamus (Romo et al., 1986a,b) similarly increases striatal dopamine levels while, at least in the latter case, inhibiting the firing of the ventral tegmental dopaminergic neurons that project to the striatum. However, glutamate antagonists infused into the striaturn tend to have no effect (Carter et al., 1988;Imperato et al., 1990;Leviel et al., 1990; Moghaddarn and Gruen, 1991; Rao et al., 1991;Keefe et al., 1992; or tend to increase extracellular dopamine levels (Barbeito et al., 1990; Moghaddarn and Gruen, 1991). Moreover, prefrontal neurons do not appear to make synaptic contact with doparninergic terminals in the striatum; rather, glutamatergic and dopaminergic terminals each synapse primarily on medium spiny neurons, often on adjacent regions of the same dendritic spine (Bouyer et al., 1984;Sesack and Pickel, 1992;Smith et al., 1994). Thus, a number of groups have begun to look for alternate avenues by which glutamatergic projections from the frontal cortex might influence dopamine levels in the striatum.The PFC sends ...

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Non-competitive antagonists are potent activators of ventral tegmental A10 dopamine neurons

Cited by 152 publications

References 12 publications

The Rapidly Acting Antidepressant Ketamine and the mGlu2/3 Receptor Antagonist LY341495 Rapidly Engage Dopaminergic Mood Circuits

The Rapidly Acting Antidepressant Ketamine and the mGlu2/3 Receptor Antagonist LY341495 Rapidly Engage Dopaminergic Mood Circuits

The Delayed Effects of DTG and MK-801 on Latent Inhibition in a Conditioned Taste-Aversion Paradigm

Increase of Extracellular Glutamate and Expression of Fos‐Like Immunoreactivity in the Ventral Tegmental Area in Response to Electrical Stimulation of the Prefrontal Cortex

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