BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine withdrawal

Pu, Lu; Liu, Qingsong; Poo, Mu‐ming

doi:10.1038/nn1687

Cited by 121 publications

(121 citation statements)

References 15 publications

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“…Amphetamine exposure increases BDNF in the BLA and within its projections to the CeA, striosomes, medial striatum and NAc (Meredith et al, 2002). BDNF potentiates psychostimulant-induced increases in DA both acutely and during sensitization (Altar et al, 1994;Pu et al, 2006;Horger et al, 1999). Conditioned place preference in response to psychostimulants is also reduced in BDNF haplodeficient mice (Hall et al, 2003).…”

Section: Bdnf In Animal Models Of Anxiety Depression and Addictionmentioning

confidence: 99%

“…Amphetamine increases TrkB expression (Meredith and Steiner, 2006) and BDNF participates in the rewarding properties of psychostimulants by potentiating pre and post synaptic activity (Horger et al, 1999). BDNF also sensitizes midbrain DA neurons to potentiation during psychostimulant withdrawal (Pu et al, 2006). A single infusion of BDNF into the VTA can potentiate cocaine craving for a month .…”

Section: Bdnf In Animal Models Of Anxiety Depression and Addictionmentioning

confidence: 99%

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Ethanol–BDNF interactions: Still more questions than answers

Davis

2008

Pharmacology & Therapeutics

127

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Brain Derived Neurotrophic Factor (BDNF) has emerged as a regulator of development, plasticity and, recently, addiction. Decreased neurotrophic activity may be involved in ethanol-induced neurodegeneration in the adult brain and in the etiology of alcohol-related neurodevelopmental disorders. This can occur through decreased expression of BDNF or through inability of the receptor to transduce signals in the presence of ethanol. In contrast, recent studies implicate region-specific up-regulation of BDNF and associated signaling pathways in anxiety, addiction and homeostasis after ethanol exposure. Anxiety and depression are precipitating factors for substance abuse and these disorders also involve region-specific changes in BDNF in both pathogenesis and response to pharmacotherapy. Polymorphisms in the genes coding for BDNF and its receptor TrkB are linked to affective, substance abuse and appetitive disorders and therefore may play a role in the development of alcoholism. This review summarizes historical and pre-clinical data on BDNF and TrkB as it relates to ethanol toxicity and addiction. Many unresolved questions about region-specific changes in BDNF expression and the precise role of BDNF in neuropsychiatric disorders and addiction remain to be elucidated. Resolution of these questions will require significant integration of the literature on addiction and comorbid psychiatric disorders that contribute to the development of alcoholism.

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Section: Bdnf In Animal Models Of Anxiety Depression and Addictionmentioning

confidence: 99%

Section: Bdnf In Animal Models Of Anxiety Depression and Addictionmentioning

confidence: 99%

Ethanol–BDNF interactions: Still more questions than answers

Davis

2008

Pharmacology & Therapeutics

127

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“…Cocaine induces TrkB-mediated signaling in the nucleus accumbens (NAc; Berhow et al 1995). Furthermore, acute cocaine administration increases striatal expression of a specific BDNF4 splice variant up to fivefold, not observed upon chronic administration, suggesting a role of specific BDNF promoter regions and regulatory sequences in stimulatory-induced alterations in BDNF expression Pu et al 2006). Administration of BDNF prevents biochemical and morphological changes associated with chronically administered cocaine and morphine, whose rewarding effects are mediated by the activation of dopamine neurons (DA) in the nucleus accumbens (NAc).…”

Section: Introductionmentioning

confidence: 99%

Role of accumbens BDNF and TrkB in cocaine-induced psychomotor sensitization, conditioned-place preference, and reinstatement in rats

et al. 2008

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Background Brain-derived neurotrophic factor (BDNF) is involved in the survival and function of midbrain DA neurons. BDNF action is mediated by the TrkB receptortyrosine kinase, and both BDNF and TrkB transcripts are widely expressed in the rat mesolimbic pathway, including the nucleus accumbens (NAc) and the ventral tegmentum area (VTA). Objective BDNF was previously shown to be involved in cocaine reward and relapse, as assessed in rat models. The goal of this study is to explore the role of BDNF and TrkB in the rat nucleus accumbens (NAc) in cocaine-induced psychomotor sensitization and in conditioned-place preference acquisition, expression, and reinstatement. Materials and methods In vivo genetic manipulations of BDNF and TrkB were performed using a lentiviral gene delivery approach to over-express these genes in the NAc and siRNA-based technology to locally knockdown gene expression. Behavioral experiments consisted of locomotor activity monitoring or cocaine-induced conditioned-place preference (CPP). Results BDNF and/or its receptor TrkB in the NAc enhance drug-induced locomotor activity and induce sensitization in rats. Furthermore, LV-BDNF-and LV-TrkB-treated rats display enhanced cocaine-induced CPP, delayed CPPextinction upon repeated measurements, and increased CPP reinstatement. In contrast, expression of TrkT1 (truncated form of TrkB, acting as a dominant negative) inhibits these behavioral changes. This inhibition is also observed when rats are fed doxycycline (to block lentivirusmediated gene expression) or when injected with siRNAsexpressing lentiviruses against TrkB. In addition, we investigate the establishment, maintenance, extinction, and reinstatement of cocaine-induced CPP. We show that BDNF and TrkB-induced CPP takes place during the learning period (conditioning), whereas extinction leads to the loss of CPP. Extinction is delayed when rats are injected LV-BDNF or LV-TrkB, and in turn, priming injections of 2 mg/kg of cocaine reinstates it. Conclusions These results demonstrate the crucial function of BDNF-through its receptor TrkB-in the enhancement of locomotor activity, sensitization, conditioned-place preference, CPP-reinstatement, and rewarding effects of cocaine in the mesolimbic dopaminergic pathway.

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“…BDNF facilitates synaptic sensitization of VTA dopamine neurons following cocaine withdrawal, which might represent a mechanism mediating cue-associated drug craving and relapse (Pu et al, 2006). Many questions remain regarding the effects of BDNF on excitability within the VTA during food reward-related processes.…”

Section: New Insights Into the Mechanisms Underlying The Effects Of Bmentioning

confidence: 99%

New Insights into the Mechanisms Underlying the Effects of BDNF on Eating Behavior

Rios

2010

Neuropsychopharmacol

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BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine withdrawal

Cited by 121 publications

References 15 publications

Ethanol–BDNF interactions: Still more questions than answers

Ethanol–BDNF interactions: Still more questions than answers

Role of accumbens BDNF and TrkB in cocaine-induced psychomotor sensitization, conditioned-place preference, and reinstatement in rats

New Insights into the Mechanisms Underlying the Effects of BDNF on Eating Behavior

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