Enhancement of Locomotor Activity and Conditioned Reward to Cocaine by Brain-Derived Neurotrophic Factor

Horger, Brian A.; Iyasere, Christiana; Berhow, Melissa T.; Messer, Chad J.; Nestler, Eric J.; Taylor, Jane R.

doi:10.1523/jneurosci.19-10-04110.1999

Cited by 343 publications

(299 citation statements)

References 71 publications

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“…Of particular interest is the observation that PCP, or its congener MK-801, modulates the cAMP response element-binding protein (CREB) transcription factor family and the brain-derived neurotrophic factor (BDNF) (Castrén et al, 1993;Hughes et al, 1993;Storvik et al, 2000). CREB and BDNF have been studied for their transient and long-lasting, respectively, roles in the reinforcing effects of drugs (Horger et al, 1999;Nestler, 2001). Moreover, it has been recently revealed that within the mesolimbic dopaminergic system, activation of CREB is associated with the dysphoric effect of early cocaine withdrawal (Pliakas et al, 2001) and BDNF induces depression-like effects (Nestler et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Spielewoy

Markou

2002

Neuropsychopharmacol

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Phencyclidine (PCP) is a drug of abuse that has rewarding and dysphoric effects in humans. The complex actions of PCP, and PCP withdrawal in particular, on brain reward function remain unclear. The purpose of the present study was to characterize the effects of withdrawal from acute and chronic PCP treatment on brain reward function in rats. A brain stimulation reward procedure was used to evaluate the effects of acute PCP injection (0, 5, or 10 mg/kg) or chronic PCP treatment (0, 10, 15, or 20 mg/kg/day for 14 days delivered via subcutaneous osmotic minipumps) on brain reward function. Withdrawal from acute administration of 5 and 10 mg/kg PCP produced a decrease in brain reward function as indicated by a sustained elevation in brain reward thresholds. When administered chronically, 10, 15, or 20 mg/kg/day PCP induced a progressive dose-dependent potentiation of brain stimulation reward, while cessation of the treatment resulted in significant elevations in reward thresholds reflecting diminished reward. Specifically, withdrawal from 15 or 20 mg/ kg/day PCP induced a depression in brain reward function that lasted for the entire month of observation. These results indicate that prolonged continuous administration of high PCP doses facilitates brain stimulation reward, while withdrawal from acute high PCP doses or chronic PCP treatment results in a protracted depression of brain reward function that may be analogous to the dysphoric and anhedonic symptoms observed in PCP dependence, depression, and schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Spielewoy

Markou

2002

Neuropsychopharmacol

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“…General methods were according to published procedures (Horger et al, 1999) and were performed in accordance with international guidelines for the ethical use of laboratory animals and the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All efforts were made to minimize animal suffering and the number of animals used.…”

Section: Methodsmentioning

confidence: 99%

Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5

et al. 2003

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Repeated exposure to cocaine produces an enduring increase in dendritic spine density in adult rat nucleus accumbens. It has been shown previously that chronic cocaine administration increases the expression of cyclin-dependent kinase-5 in this brain region and that this neuronal protein kinase regulates cocaine-induced locomotor activity. Moreover, cyclin-dependent kinase-5 has been implicated in neuronal function and synaptic plasticity. Therefore, we studied the involvement of this enzyme in cocaine's effect on dendritic spine density. Adult male rats, receiving intra-accumbens infusion of the cyclin-dependent kinase-5 inhibitor roscovitine or saline, were administered a 28-day cocaine treatment regimen. Animals were killed 24-48 h after the final cocaine injection and their brains removed and processed for Golgi-Cox impregnation. Our findings demonstrate that roscovitine attenuates cocaine-induced dendritic spine outgrowth in nucleus accumbens core and shell and such inhibition reduces spine density in nucleus accumbens shell of control animals. These data indicate that cyclin-dependent kinase-5 is involved in regulation of, as well as cocaine-induced changes in, dendritic spine density. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2015 January 16. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptLong-term exposure to psychostimulant drugs produces enduring neuronal alterations in intracellular signaling pathways and structural changes in dendritic morphology (Nestler, 2001). For example, repeated exposure to cocaine increases spine density on dendrites of dopaminoceptive medium spiny neurons in the shell (but not core) division of nucleus accumbens (NAc) (Robinson and Kolb, 1999;Robinson et al., 2001) and increases the expression of several transcription factors that mediate gene expression in these neurons (Nestler, 2001). Recently, cyclin-dependent kinase-5 (Cdk5) was identified as a downstream target of the transcription factor ΔFosB which is persistently expressed in NAc of mice repeatedly treated with cocaine. Overexpression of ΔFosB increases Cdk5 expression and activity (Kelz et al., 1999;Bibb et al., 2001). Cdk5 is a protein serine/threonine kinase that regulates neurite outgrowth (Dhavan and Tsai, 2001) and modulates dopamine signaling (Bibb et al., 1999a). Interestingly, acute inhibition of Cdk5 activity in NAc potentiates the locomotor effects of chronic cocaine (Bibb et al., 2001). The purpose of the present study was to determine if this neuronal protein kinase is involved in cocaine-induced dendritic spine proliferation in rat NAc.The potent Cdk5 inhibitor roscovitine (or vehicle) was bilaterally infused into NAc shell via ALZET mini-pump. The effect of a 4-week regimen of repeated i.p. injections of cocaine (or saline) on dendritic spine density was assessed by a modified Golgi staining technique. Detailed anatomical features along dendrites were easily discernible and dendritic spines were readily resolved (Fig. 1). Re...

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“…In addition, early phases of instrumental learning (Hernandez et al 2006;Kelly and Deadwyler 2003) elicit widespread zif/268 and arc induction throughout an extensive corticostriatal network in rats, whereas manipulation of BDNF levels in the brain alters cocaine-seeking in a regionally selective manner (Horger et al 1999;Lu et al 2004;Berglind et al 2007;Graham et al 2007). …”

Section: Functional Significance Of Gene Expression Changesmentioning

confidence: 99%

“…Furthermore, manipulation of BDNF levels in the brain alters cocaine seeking (Horger et al 1999;Lu et al 2004;Berglind et al 2007;Graham et al 2007). Additionally, early phases of instrumental learning (Hernandez et al 2006;Kelly and Deadwyler 2003) elicit widespread zif/268 and arc induction throughout an extensive corticostriatal network in rats.…”

mentioning

confidence: 99%

Relapse to cocaine seeking increases activity-regulated gene expression differentially in the prefrontal cortex of abstinent rats

et al. 2008

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Rationale-Alterations in the activity of the prefrontal and orbitofrontal cortices of cocaine addicts have been linked with re-exposure to cocaine-associated stimuli. Objectives Using an animal model of relapse to cocaine seeking, the present study investigated the expression patterns of four different activity-regulated genes within prefrontal cortical brain regions after 22 h or 15 days of abstinence during context-induced relapse.Materials and methods-Rats self-administered cocaine or received yoked-saline for 2 h/day for 10 days followed by 22 h or 2 weeks of abstinence when they were re-exposed to the selfadministration chamber with or without levers available to press for 1 h. Brains were harvested and sections through the prefrontal cortex were processed for in situ hybridization using radioactive oligonucleotide probes encoding c-fos, zif/268, arc, and bdnf.Results-Re-exposure to the chamber in which rats previously self-administered cocaine but not saline, regardless of lever availability, increased the expression of all genes in the medial prefrontal and orbitofrontal cortices at both time points with one exception: bdnf mRNA was significantly increased in the medial prefrontal cortex at 22 h only if levers previously associated with cocaine delivery were available to press. Furthermore, re-exposure of rats to the chambers in which they received yoked saline enhanced both zif/268 and arc expression selectively in the orbito-frontal cortex after 15 days of abstinence.Correspondence to: J. F. McGinty. HHS Public AccessAuthor manuscript Psychopharmacology (Berl). Author manuscript; available in PMC 2017 May 22. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptConclusions-These results support convergent evidence that cocaine-induced changes in the prefrontal cortex are important in regulating drug seeking following abstinence and may provide additional insight into the molecular mechanisms involved in these processes. KeywordsAddiction; Arc; BDNF; c-fos; Relapse; zif/268; Self-administration; Abstinence; ExtinctionRelapse to drug seeking and taking in addicted humans is often triggered by re-exposure to environmental cues previously associated with the drug (Ehrman et al. 1992). Similarly, in animal studies, during chronic drug self-administration, the drug-paired environment acquires conditioned reinforcing properties that trigger drug-seeking behavior upon reexposure to the context following forced abstinence (Crombag and Shaham 2002;Fuchs et al. 2005Fuchs et al. , 2006. Thus, like other forms of learning, relapse to drug-seeking involves the formation and retrieval of instrumental memories (Hyman 2005). A major question in addiction research is whether the neural substrates underlying drug-seeking involve the same cell signaling and synaptic plasticity processes within the same brain regions as those implicated in other forms of reward learning and memory (Berke and Hyman 2000;Hyman and Malenka 2001;Nestler 2001).The inhibitory control functions of the prefrontal cortical ...

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Enhancement of Locomotor Activity and Conditioned Reward to Cocaine by Brain-Derived Neurotrophic Factor

Cited by 343 publications

References 71 publications

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5

Relapse to cocaine seeking increases activity-regulated gene expression differentially in the prefrontal cortex of abstinent rats

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