Chemical Stimulation of the Ventral Hippocampus Elevates Nucleus Accumbens Dopamine by Activating Dopaminergic Neurons of the Ventral Tegmental Area

Legault, Mark; Rompré, Pierre‐Paul; Wise, Roy A.

doi:10.1523/jneurosci.20-04-01635.2000

Cited by 182 publications

(157 citation statements)

References 54 publications

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“…Indeed, at the dose that decreased cocaine-primed reinstatement, KYN also decreased cocaine SA. Intra-VTA KYN blocks the activation of VTA DA neurons induced by electrical stimulation of the BNST or chemical stimulation of the vSUB (Legault et al, 2000;Georges and Aston-Jones, 2002). In addition, the same studies demonstrate that the increase in DA efflux in the NAcc induced by chemical stimulation of the vSUB is blocked by intra-VTA KYN and that intra-VTA KYN alone does not increase either VTA DA neuronal activity or DA efflux in the NAcc.…”

Section: Discussionmentioning

confidence: 75%

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

Sun

Akins

Mattingly

et al. 2005

Neuropsychopharmacol

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Drug addiction is characterized by compulsive drug-seeking and drug-taking behavior and by a high rate of relapse even after long periods of abstinence. Although the mesocorticolimbic dopamine (DA) pathway is thought to play a critical role in drug craving and relapse, recent evidence also implicates glutamate, an amino acid known to activate DA neurons in the ventral tegmental area (VTA) via ionotropic receptors. To assess whether increased glutamate transmission in the VTA is involved in cocaine-primed drug-seeking behavior, we tested rats in a between-session reinstatement model. They were trained to press a lever for cocaine infusions (0.25 mg/ infusion) accompanied by compound stimuli (light and tone) under a modified fixed-ratio 5 reinforcement schedule. Cocaine-primed reinstatement was conducted after lever pressing was extinguished in the absence of the conditioned stimuli. Blockade of ionotropic glutamate receptors in the VTA by local application of kynurenate (0.0, 1.0, 3.2, and 5.6 mg/side) dose-dependently decreased cocaineprimed reinstatement, whereas sucrose-primed reinstatement of sucrose-seeking behavior was unaffected. In addition, the minimum effective dose for decreasing cocaine-primed reinstatement was ineffective in the substantia nigra. Together, these data indicate that glutamatergic activation of the VTA is critical for cocaine-primed reinstatement. Because such activation can increase impulse flow in DA neurons and thus DA release in mesocorticolimbic targets, this glutamate-DA interaction in the VTA may underlie cocaine-primed relapse to cocaine-seeking behavior.

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Section: Discussionmentioning

confidence: 75%

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

Sun

Akins

Mattingly

et al. 2005

Neuropsychopharmacol

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“…Projections from the SUB to the two subregions of the nucleus accumbens have been described, although the SUB appears to reach predominantly the dorsomedial shell subregion (Brog et al, 1993;Groenewegen et al, 1987Groenewegen et al, , 1999Mulder et al, 1998). Regulation of dopamine release and metabolism in the nucleus accumbens by SUB projections has been reported for both the core and dorsomedial shell parts in adult animals (Louilot and Le Moal, 1994;Blaha et al, 1997;Legault and Wise, 1999;Legault et al, 2000;Taepavarapruk et al, 2000;Floresco et al, 2001;Cano-Cebrian et al, 2003). Previous data showed that unlike the SUB, neonatal blockade of the ENT induced a complete disruption of the typical latent inhibition-related dopaminergic responses in both the core and in the dorsomedial shell parts of the nucleus accumbens (Peterschmitt et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Latent Inhibition-Related Dopaminergic Responses in the Nucleus Accumbens are Disrupted Following Neonatal Transient Inactivation of the Ventral Subiculum

Meyer

Louilot

2011

Neuropsychopharmacol

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Schizophrenia would result from a defective connectivity between several integrative regions as a consequence of neurodevelopmental failure. Various anomalies reminiscent of early brain development disturbances have been observed in patients' left ventral subiculum of the hippocampus (SUB). Numerous data support the hypothesis of a functional dopaminergic dysregulation in schizophrenia. The common target structure for the action of antipsychotics appears to be a subregion of the ventral striatum, the dorsomedial shell part of the nucleus accumbens. Latent inhibition, a cognitive marker of interest for schizophrenia, has been found to be disrupted in acute patients. The present study set out to investigate the consequences of a neonatal functional inactivation of the left SUB by tetrodotoxin (TTX) in 8-day-old rats for the latent inhibition-related dopaminergic responses, as monitored by in vivo voltammetry in freely moving adult animals (11 weeks) in the left core and dorsomedial shell parts of the nucleus accumbens in an olfactory aversion procedure. Results obtained during the retention session of a threestage latent inhibition protocol showed that the postnatal unilateral functional blockade of the SUB was followed in pre-exposed TTXconditioned adult rats by a disruption of the behavioral expression of latent inhibition and induced a total and a partial reversal of the latent inhibition-related dopaminergic responses in the dorsomedial shell and core parts of the nucleus accumbens, respectively. The present data suggest that neonatal inactivation of the SUB has more marked consequences for the dopaminergic responses recorded in the dorsomedial shell part, than in the core part of the nucleus accumbens. These findings may provide new insight into the pathophysiology of schizophrenia.

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“…In the case of ventral subiculum stimulation, it was furthermore shown that comparable reinstatement effects could be obtained by intra-VTA infusion of NMDA, and that stimulation-induced reinstatement is completely blocked by microinfusion of kynurenic acid into the VTA. 95 Stimulation of the ventral subiculum enhances firing of dopamine neurons in the VTA and increases dopamine release in the NAS 12,96 that similarly can be blocked by intra-VTA infusion of kynurenic acid. Since dopamine can also produce reinstatement when injected into the NAS, 15 these findings, taken together, would suggest that stimulation of the ventral subiculum activates glutamatergic projections to the VTA which in turn activates the dopaminergic projection to the NAS, increasing dopamine release which would then trigger relapse.…”

Section: Role Of Glutamate In Drug-craving Reinstatement and Relapsementioning

confidence: 99%

Glutamatergic mechanisms in addiction

2003

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Traditionally, addiction research in neuroscience has focused on mechanisms involving dopamine and endogenous opioids. More recently, it has been realized that glutamate also plays a central role in processes underlying the development and maintenance of addiction. These processes include reinforcement, sensitization, habit learning and reinforcement learning, context conditioning, craving and relapse. In the past few years, some major advances have been made in the understanding of how glutamate acts and interacts with other transmitters (in particular, dopamine) in the context of processes underlying addiction. It appears that while many actions of glutamate derive their importance from a stimulatory interaction with the dopaminergic system, there are some glutamatergic mechanisms that contribute to addiction independent of dopaminergic systems. Among those, context-specific aspects of behavioral determinants (ie control over behavior by conditioned stimuli) appear to depend heavily on glutamatergic transmission. A better understanding of the underlying mechanisms might open new avenues to the treatment of addiction, in particular regarding relapse prevention.

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Chemical Stimulation of the Ventral Hippocampus Elevates Nucleus Accumbens Dopamine by Activating Dopaminergic Neurons of the Ventral Tegmental Area

Cited by 182 publications

References 54 publications

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

Latent Inhibition-Related Dopaminergic Responses in the Nucleus Accumbens are Disrupted Following Neonatal Transient Inactivation of the Ventral Subiculum

Glutamatergic mechanisms in addiction

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