Evidence of a complete independence of the neurobiological substrates for the induction and expression of behavioral sensitization to amphetamine

Cador, Martine; Bjijou, Y; Stinus, L.

doi:10.1016/0306-4522(94)00524-9

Cited by 267 publications

(164 citation statements)

References 34 publications

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“…AMPH appears to produce these long-lasting effects by acting in the VTA. Infusions of the drug into this site have been shown to produce locomotor sensitization to AMPH (Perugini and Vezina, 1994;Cador et al, 1995) and cocaine (Kalivas and Weber, 1988), NAcc DA sensitization to AMPH (Vezina, 1993(Vezina, , 1996, as well as enhanced AMPH and cocaine ; present study) self-administration. Conversely, sensitized locomotor responding to AMPH and cocaine (Kalivas and Weber, Figure 3.…”

Section: Amph Acts In the Vta To Induce Psychostimulant Sensitizationsupporting

confidence: 51%

“…Exposure to AMPH enhances cocaine self-administration N Suto et al 1988; Hooks et al, 1992;Cador et al, 1995) and enhanced AMPH self-administration are not produced when animals are pre-exposed to AMPH in DA neuron terminal regions such as the NAcc. Overall, this evidence indicates that AMPH acts in the VTA not only to produce sensitized locomotor and NAcc DA responding to psychostimulants but also to enhance the self-administration of these drugs.…”

Section: Neuropsychopharmacologymentioning

confidence: 99%

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Previous Exposure to VTA Amphetamine Enhances Cocaine Self-Administration under a Progressive Ratio Schedule in an NMDA, AMPA/Kainate, and Metabotropic Glutamate Receptor-Dependent Manner

Suto

Tanabe

Austin

et al. 2003

Neuropsychopharmacol

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Previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) enhances cocaine self-administration in a D 1 dopamine receptor-dependent manner. The present study examined the contribution of VTA NMDA, AMPA/kainate, and metabotropic glutamate (mGlu) receptors to this effect. Rats in different groups received three intra-VTA injections, one every third day, of either saline (0.5 ml/ side), AMPH (2.5 mg/0.5 ml/side), AMPH+CPP (NMDA receptor antagonist; 10 mM or 100 mM/0.5 ml/side), AMPH+CNQX (AMPA/ kainate receptor antagonist; 0.3 mM or 1 mM/0.5 ml/side), AMPH+MCPG (mGlu receptor antagonist; 0.5 mM or 50 mM/0.5 ml/side), or the glutamate receptor antagonists alone. Starting 7-10 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.3 mg/kg/infusion) and then tested under a progressive ratio (PR) schedule of reinforcement for 6 consecutive days. As reported previously, VTA AMPH pre-exposed rats worked more and obtained more infusions of cocaine than saline pre-exposed animals. Coadministration of CPP, CNQX, or MCPG with AMPH during pre-exposure dose-dependently blocked this enhancement of cocaine self-administration. Rats pre-exposed to the glutamate receptor antagonists alone did not differ on the test days from the saline pre-exposed controls. These results indicate that, in a manner paralleling the induction of sensitization of the locomotor stimulating effects of AMPH, activation of NMDA, AMPA/kainate, and mGlu receptors during pre-exposure to AMPH in the VTA is necessary for the enhancement of cocaine self-administration to develop.

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Section: Amph Acts In the Vta To Induce Psychostimulant Sensitizationsupporting

confidence: 51%

Section: Neuropsychopharmacologymentioning

confidence: 99%

Previous Exposure to VTA Amphetamine Enhances Cocaine Self-Administration under a Progressive Ratio Schedule in an NMDA, AMPA/Kainate, and Metabotropic Glutamate Receptor-Dependent Manner

Suto

Tanabe

Austin

et al. 2003

Neuropsychopharmacol

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“…We cannot rule out that the intact brain is required for potentiation. However, previous work demonstrated that local injection of amphetamine into the VTA in vivo is sufficient to trigger sensitization (Vezina, 1993;Cador et al, 1995). We therefore speculate that amphetamine can directly trigger LTP within the VTA in vivo because sufficient levels of glutamatergic synaptic activity are present, but that in our slice experiments levels of synaptic activity are too low to trigger LTP.…”

Section: In Vitro Exposure To Amphetamine Does Not Trigger Ltpmentioning

confidence: 49%

“…Thus, considerable effort has been directed at studying the mechanisms responsible for behavioral sensitization. Local effects of drugs of abuse on VTA neurons appear to be necessary and sufficient to trigger sensitization, because repeated local microinjections of amphetamine or morphine into the VTA elicit behavioral sensitization (Kalivas and Duffy, 1987;Kalivas and Weber, 1988;Druhan et al, 1993;Vezina, 1993;Cador et al, 1995) and microinjections of specific DA or glutamate receptor antagonists into the VTA prevent sensitization (Vezina and Stewart, 1989;Kalivas and Alesdatter, 1993;Bjijou et al, 1996;Kim and Vezina, 1998;Cador et al, 1999;Vezina and Queen, 2000). Several lines of evidence support the idea that synaptic plasticity at glutamate synapses in the VTA plays a key role in triggering sensitization and other neuroadaptations that may contribute to the development of addiction (Schenk and Snow, 1994;White, 1996;Carlezon et al, 1997;Ungless et al, 2001;Hyman and Malenka, 2001;Kauer, 2004).…”

Section: Introductionmentioning

confidence: 99%

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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Drugs of abuse activate the reward circuitry of the mesocorticolimbic system, and it has been hypothesized that drug exposure triggers synaptic plasticity of glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area. Here, we show that just a 2 h in vivo exposure to amphetamine is sufficient to potentiate these synapses, measured as an increase in the synaptic AMPAR/NMDAR ratio. We tested the prediction that an increase in GluR1-containing AMPA receptors would result in an increase in GluR1 homomeric receptors at synapses, but were unable to observe any evidence of the predicted rectification in DA neurons from animals treated with amphetamine. We also examined the possibility of increased AMPA receptor insertion in the membrane, but did not detect a significant increase in biotinylated surface GluR1. We conclude that amphetamine induces rapid changes in synaptic AMPAR/NMDAR ratios, suggesting that potentiation of glutamatergic synapses is a relatively early event in the series of neuroadaptations in response to drugs of abuse.

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“…Thus, the differential response to amphetamine does not result from alterations in basal activity levels. As the acute effects of amphetamine on locomotor activity are largely mediated by amphetamine-induced DA release in the Nacc, [22][23][24] it is possible to speculate that the blunted response to amphetamine observed in dcc heterozygotes results from decreased mesoaccumbens DA transmission. Several lines of evidence indicate that DA neurons that project to the NAcc (mesolimbic) have anatomical and functional characteristics that are distinct from those that project to the mPFC (mesocortical).…”

Section: Discussionmentioning

confidence: 99%

Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine

et al. 2004

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Netrins are guidance cues that play a fundamental role in organizing the developing brain. The netrin receptor, DCC (deleted in colorectal cancer), is highly expressed by dopaminergic (DA) neurons. DCC may therefore participate in the organization of DA circuitry during development and also influence DA function in the adult. Here we show that adult dcc heterozygous mice exhibit a blunted behavioral response to the indirect DA agonist amphetamine and do not develop sensitization to its effects when treated repeatedly. These behavioral alterations are associated with profound changes in DA function. In the medial prefrontal cortex, dcc heterozygotes exhibit increased tyrosine hydroxylase (TH) protein levels and dramatic increases in basal concentrations of DA and DA metabolites. In contrast, in the nucleus accumbens, dcc heterozygotes show no changes in either TH or DA levels, but exhibit decreased concentrations of DA metabolites, suggesting reduced DA activity. In addition, dcc heterozygous mice exhibit a small, but significant reduction in total number of TH-positive neurons in midbrain DA cell body regions. These results demonstrate for the first time that alterations in dcc expression lead to selective changes in DA function and, in turn, to differences in DA-related behaviors in adulthood. These findings raise the possibility that changes in dcc function early in life are implicated in the development of DA dysregulation observed in certain psychiatric disorders, such as schizophrenia, or following chronic use of drugs of abuse. Keywords: axon guidance; DCC; prefrontal cortex; schizophrenia; drug abuse; psychostimulant drugs Repeated exposure to stimulant drugs, such as amphetamine, leads to the development of increased sensitivity to the behavioral-activating effects of these drugs. This phenomenon, known as behavioral sensitization, is long-lasting and is accompanied by enhanced stimulant-induced dopamine (DA) release in the nucleus accumbens (NAcc). 1,2 Individual differences in susceptibility to the effects of stimulants on behavior and on the release of DA have been demonstrated in both humans and adult laboratory animals. [3][4][5][6][7][8] Although the processes that lead to differences in vulnerability to stimulant drugs remain to be elucidated, evidence indicates that both genetic factors 9 and exposure to environmental insults early in life are involved. 10 Perinatal insults can result in sensitized behavioral and mesolimbic DA responses of adult rats to an acute injection of amphetamine. 11 Similarly, lesions of forebrain structures made in neonatal rats lead to enhanced behavioral responses to amphetamine in adult animals. 5,12 These findings suggest that anomalies in the development and organization of DA circuitry contribute to subsequent functional and behavioral abnormalities in the adult. However, little is known about the molecular mechanisms that regulate the development of DA systems.Netrins are a family of secreted proteins that play a fundamental role in the organization of the develop...

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Evidence of a complete independence of the neurobiological substrates for the induction and expression of behavioral sensitization to amphetamine

Cited by 267 publications

References 34 publications

Previous Exposure to VTA Amphetamine Enhances Cocaine Self-Administration under a Progressive Ratio Schedule in an NMDA, AMPA/Kainate, and Metabotropic Glutamate Receptor-Dependent Manner

Previous Exposure to VTA Amphetamine Enhances Cocaine Self-Administration under a Progressive Ratio Schedule in an NMDA, AMPA/Kainate, and Metabotropic Glutamate Receptor-Dependent Manner

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine

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