Basic fibroblast growth factor as a mediator of the effects of glutamate in the development of long-lasting sensitization to stimulant drugs: studies in the rat

Flores, Cecilia; Stewart, Jane

doi:10.1007/s002130000417

Cited by 62 publications

(40 citation statements)

References 151 publications

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“…Exposure to AMPH enhances cocaine self-administration N Suto et al sensitization normally observed in the VTA such as D 2 DA autoreceptor subsensitivity (Wolf et al, 1994) and increased basic fibroblast growth factor, which through its effects on astrocytic function may affect the function of dopaminergic neurons (Flores and Stewart, 2000). The present results are consistent with these findings.…”

Section: Induction Of Sensitization By Amph Requires Activation Of Glsupporting

confidence: 90%

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: Induction Of Sensitization By Amph Requires Activation Of Glsupporting

confidence: 90%

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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“…Following repeated cocaine injections or self-administration, increased numbers of dendritic spines and spine density are observed in reward-related brain regions such as the PFC Kolb, 1997, 1999;Robinson et al, 2001). Such structural changes could be regulated by neurotrophic factors, such as bFGF, as they promote neuron differentiation, neurogenesis, and experience-dependent plasticity (Aoyagi et al, 1994;Wagner et al, 1999;Flores and Stewart, 2000b). Following chronic or acute cocaine administration, bFGF mRNA expression is increased in reward-related brain regions such as the PFC (Fumagalli et al, 2006), and we showed that bFGF protein expression is similarly increased in IL-mPFC following cocaine self-administration.…”

Section: Discussionmentioning

confidence: 99%

“…Stimulant drug use results in structural and functional changes in reward-related brain regions (Flores and Stewart, 2000b;Pickens et al, 2011). For example, expansion of dendritic arbors on dopaminergic neurons in the ventral tegmental area (VTA) occurs following stimulant drug administration (Mueller et al, 2006), and both dendritic length and spine density are increased in the prefrontal cortex (PFC) and nucleus accumbens following prolonged withdrawal Kolb, 1997, 1999).…”

Section: Introductionmentioning

confidence: 99%

Blocking Infralimbic Basic Fibroblast Growth Factor (bFGF or FGF2) Facilitates Extinction of Drug Seeking After Cocaine Self-Administration

Hafenbreidel

Twining

Todd

et al. 2015

Neuropsychopharmacol

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Drug exposure results in structural and functional changes in brain regions that regulate reward and these changes may underlie the persistence of compulsive drug seeking and relapse. Neurotrophic factors, such as basic fibroblast growth factor (bFGF or FGF2), are necessary for neuronal survival, growth, and differentiation, and may contribute to these drug-induced changes. Following cocaine exposure, bFGF is increased in addiction-related brain regions, including the infralimbic medial prefrontal cortex (IL-mPFC). The IL-mPFC is necessary for extinction, but whether drug-induced overexpression of bFGF in this region affects extinction of drug seeking is unknown. Thus, we determined whether blocking bFGF in IL-mPFC would facilitate extinction following cocaine self-administration. Rats were trained to lever press for intravenous infusions of cocaine before extinction. Blocking bFGF in IL-mPFC before four extinction sessions resulted in facilitated extinction. In contrast, blocking bFGF alone was not sufficient to facilitate extinction, as blocking bFGF and returning rats to their home cage had no effect on subsequent extinction. Furthermore, bFGF protein expression increased in IL-mPFC following cocaine self-administration, an effect reversed by extinction. These results suggest that cocaine-induced overexpression of bFGF inhibits extinction, as blocking bFGF during extinction permits rapid extinction. Therefore, targeted reductions in bFGF during therapeutic interventions could enhance treatment outcomes for addiction.

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“…These molecules are differentially expressed in the bHR and bLR rat lines (19,29) and have been previously implicated in addiction-related behaviors (e.g., refs. [30][31][32]. We have shown that administration of FGF2 early in life increases the acquisition of cocaine self-administration in adulthood (33) and renders bLRs more bHR-like (34), supporting a role for FGF2 as a neuromolecular antecedent of drugtaking behavior (18,35).…”

mentioning

confidence: 81%

Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model

Flagel

Chaudhury

Waselus

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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This study provides a demonstration in the rat of a clear genetic difference in the propensity for addiction-related behaviors following prolonged cocaine self-administration. It relies on the use of selectively bred high-responder (bHR) and low-responder (bLR) rat lines that differ in several characteristics associated with "temperament," including novelty-induced locomotion and impulsivity. We show that bHR rats exhibit behaviors reminiscent of human addiction, including persistent cocaine-seeking and increased reinstatement of cocaine seeking. To uncover potential underlying mechanisms of this differential vulnerability, we focused on the core of the nucleus accumbens and examined expression and epigenetic regulation of two transcripts previously implicated in bHR/ bLR differences: fibroblast growth factor (FGF2) and the dopamine D2 receptor (D2). Relative to bHRs, bLRs had lower FGF2 mRNA levels and increased association of a repressive mark on histones (H3K9me3) at the FGF2 promoter. These differences were apparent under basal conditions and persisted even following prolonged cocaine self-administration. In contrast, bHRs had lower D2 mRNA under basal conditions, with greater association of H3K9me3 at the D2 promoter and these differences were no longer apparent following prolonged cocaine self-administration. Correlational analyses indicate that the association of H3K9me3 at D2 may be a critical substrate underlying the propensity to relapse. These findings suggest that low D2 mRNA levels in the nucleus accumbens core, likely mediated via epigenetic modifications, may render individuals more susceptible to cocaine addiction. In contrast, low FGF2 levels, which appear immutable even following prolonged cocaine exposure, may serve as a protective factor. addiction | dopamine | fibroblast growth factor | nucleus accumbens | reinstatement A pproximately 16% of adults in the United States report drug use within the past year (1). However, not everyone who experiments with drugs becomes an addict, as an estimated 8.5% of the population, or 25 million Americans, meet Diagnostic and Statistical Manual of Mental Disorders IV (2) criteria for substance abuse and dependence (1). Environmental and societal factors play a role in addiction liability (e.g., refs. 3-5), and there is ample evidence demonstrating a role for genetic factors (e.g., refs. 6-10). However, studying the interplay among these factors is difficult in human studies because of the inability to control for environmental factors and the challenge of parsing causes from consequences. Preclinical animal models are therefore essential for defining the complex interactions between genes and environment, and uncovering the neural mechanisms that might render an individual more susceptible to drug addiction. The first animal model characterizing individual differences in the propensity to take drugs of abuse was introduced over two decades ago by Piazza et al. (11), who showed that, like humans, only some rats readily self-administer such drugs. Furthermore...

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Basic fibroblast growth factor as a mediator of the effects of glutamate in the development of long-lasting sensitization to stimulant drugs: studies in the rat

Cited by 62 publications

References 151 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

Blocking Infralimbic Basic Fibroblast Growth Factor (bFGF or FGF2) Facilitates Extinction of Drug Seeking After Cocaine Self-Administration

Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model

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