Conditioned place preference for cocaine is attenuated in mice over-expressing the 5-HT 3 receptor

Only a sub-group of human drug users progress from initial drug-taking to drug addiction. An important aspect of this progression is the influence of the learned association between the effects of the drug and the environment in which it is experienced on continued drug-taking and-seeking. These associations can be modeled using the conditioned place preference (CPP) paradigm, although no current method of CPP analysis allows for identification of within-group variability among subjects. In the present study, we adapted a “criterion” method of analysis to separate “CPP expressing” from “non-CPP expressing” rats, in order to study more directly within-group variability in the CPP paradigm. Male Sprague-Dawley rats were conditioned with cocaine (5, 10, 20 mg/kg) or saline in an unbiased three-chamber CPP apparatus in either a single- or four-trial CPP procedure. A classification and regression tree analysis of time spent in the cocaine-paired chamber established a time of 324 s spent in the cocaine-paired chamber as the criterion for cocaine CPP expression. This criterion effectively discriminated control from cocaine-conditioned rats and was reliable for rats trained in both a single- and four-trial CPP procedure. The criterion method showed an enhanced ability to detect effective doses of cocaine in the single trial procedure and a blockade of CPP expression by MK 212 (0.125 mg/kg) treatment in a sub-group of rats. These data support the utility of the criterion analysis as an adjunct to traditional methods that compare group averages in CPP.

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“…2005) or amphetamine (Mead et al . 1999), although exceptions to the all-or-none dose-effect function have been observed (Allan et al . 2001).…”

Section: Discussionmentioning

confidence: 99%

Novel approach to data analysis in cocaine-conditioned place preference

Cruz

Herin

Grady

et al. 2009

Behavioural Pharmacology

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“…For cocaine CPP, 2 month old Male C57Bl/6J mice underwent training as previously described ( Allan et al, 2001 ; Oliver et al, 2018 ). Mice were sacrificed 1 h after testing and the nucleus accumbens (NAc) was collected.…”

Section: Methodsmentioning

confidence: 99%

HuD Binds to and Regulates Circular RNAs Derived From Neuronal Development- and Synaptic Plasticity-Associated Genes

2020

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The RNA-binding protein (RBP) HuD is involved in neuronal differentiation, regeneration, synaptic plasticity and learning and memory. RBPs not only bind to mRNAs but also interact with several types of RNAs including circular RNAs (circRNAs), a class of non-coding RNAs generated by pre-mRNA back-splicing. This study explored whether HuD could regulate the expression of neuronal circRNAs. HuD controls target RNA’s fate by binding to Adenylate-Uridylate Rich Elements (AREs). Using bioinformatics analyses, we found HuD-binding ARE-motifs in about 26% of brain-expressed circRNAs. By RNA immunoprecipitation (RIP) from the mouse striatum followed by circRNA arrays, we identified over 600 circRNAs bound to HuD. Among these, 226 derived from genes where HuD also bound to their associated mRNAs including circHomer1a , which we previously characterized as a synaptic HuD target circRNA. Binding of HuD to two additional plasticity–associated circRNAs, circCreb1 , and circUfp2 , was validated by circRNA-specific qRT-PCR. Interestingly, we found that circUpf2 is also enriched in synaptosomes. Pathway analyses confirmed that the majority of HuD-bound circRNAs originate from genes regulating nervous system development and function. Using striatal tissues from HuD overexpressor (HuD-OE) and knock out (KO) mice for circRNA expression analyses we identified 86 HuD-regulated circRNAs. These derived from genes within the same biological pathways as the HuD RIP. Cross-correlation analyses of HuD-regulated and HuD-bound circRNAs identified 69 regulated in either HuD-OE or HuD-KO and 5 in both sets. These include circBrwd1 , circFoxp1 , and circMap1a , which derive from genes involved in neuronal development and regeneration, and circMagi1 and circLppr4 , originating from genes controlling synapse formation and linked to psychiatric disorders. These circRNAs form competing endogenous RNA (ceRNA) networks including microRNAs and mRNAs. Among the HuD target circRNAs, circBrwd1 and circFoxp1 are regulated in an opposite manner to their respective mRNAs. The expressions of other development- and plasticity-associated HuD target circRNAs such as circSatb2, cirHomer1a and circNtrk3 are also altered after the establishment of cocaine conditioned place preference (CPP). Collectively, these data suggest that HuD interactions with circRNAs regulate their expression and transport, and that the ensuing changes in HuD-regulated ceRNA networks could control neuronal differentiation and synaptic plasticity.

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“…Moreover, in 5-HT 3 receptors over-expressed mice, the DA release induced by a 5-HT 3 receptor agonist was increased compared to wild type [143]. Similarly, dorsal raphe nucleus stimulation increases DA release in nucleus accumbens which is attenuated by a 5-HT 3 receptor antagonist [133].…”

Section: Effect Of 5-ht3 Receptor Ligands On Neuronal Firing and Neurmentioning

confidence: 99%

Role of 5-HT3 Receptors in the Antidepressant Response

et al. 2011

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Serotonin (5-HT)3 receptors are the only ligand-gated ion channel of the 5-HT receptors family. They are present both in the peripheral and central nervous system and are localized in several areas involved in mood regulation (e.g., hippocampus or prefrontal cortex). Moreover, they are involved in regulation of neurotransmitter systems implicated in the pathophysiology of major depression (e.g., dopamine or GABA). Clinical and preclinical studies have suggested that 5-HT3 receptors may be a relevant target in the treatment of affective disorders. 5-HT3 receptor agonists seem to counteract the effects of antidepressants in non-clinical models, whereas 5-HT3 receptor antagonists, such as ondansetron, present antidepressant-like activities. In addition, several antidepressants, such as mirtazapine, also target 5-HT3 receptors. In this review, we will report major advances in the research of 5-HT3 receptor's roles in neuropsychiatric disorders, with special emphasis on mood and anxiety disorders.

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Conditioned place preference for cocaine is attenuated in mice over-expressing the 5-HT 3 receptor

Cited by 38 publications

References 1 publication

Novel approach to data analysis in cocaine-conditioned place preference

Novel approach to data analysis in cocaine-conditioned place preference

HuD Binds to and Regulates Circular RNAs Derived From Neuronal Development- and Synaptic Plasticity-Associated Genes

Role of 5-HT3 Receptors in the Antidepressant Response

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