Cocaine differentially affects synaptic activity in memory and midbrain areas of female and male rats: an in vivo MEMRI study

Pérez, Pablo D.; Hall, Gabrielle; Zubcevic, Jasenka; Febo, Marcelo

doi:10.1007/s11682-017-9691-1

Cited by 13 publications

(11 citation statements)

References 97 publications

(126 reference statements)

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“…With both MnCl 2 administration procedures regional distribution of T1 reduction is consistent with previous research 25 , 52 .…”

Section: Resultssupporting

confidence: 91%

“…Detailed T1 reductions are showed in Supporting Information Table S1. With both MnCl 2 administration procedures regional distribution of T1 reduction is consistent with previous research 25,52 . Figure 1.…”

Section: Resultssupporting

confidence: 90%

“…Previous studies have also used MEMRI to examine cocaine-induced brain activation. Lu and co-workers tested the effect of an acute cocaine injection in naïve rats and found increased activity brain-wide 24 ; others have used MEMRI to study cocaine-induced behavioral sensitization 26 and sex differences in cocaine-induced brain activation 25 . All of these previous studies have used either acute cocaine treatment or relatively short repeated treatments, and cocaine experience was always non-contingently (i.e.…”

Section: Discussionmentioning

confidence: 99%

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Cocaine addicted rats show reduced neural activity as revealed by manganese-enhanced MRI

Cannella

Cosa‐Linan

Takahashi

et al. 2020

Sci Rep

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Cocaine addiction develops as a continuum from recreational to habitual and ultimately compulsive drug use. Cocaine addicts show reduced brain activity. However, it is not clear if this condition results from individual predisposing traits or is the result of chronic cocaine intake. A translational neuroimaging approach with an animal model distinguishing non-addict-like vs. addict-like animals may help overcome the limitations of clinical research by comparing controlled experimental conditions that are impossible to obtain in humans. Here we aimed to evaluate neuronal activity in freely moving rats by manganese enhanced magnetic resonance imaging in the 0/3crit model of cocaine addiction. We show that addict-like rats exhibit reduced neuronal activity compared to cocaine-naïve controls during the first week of abstinence. In contrast, cocaine-experienced non-addict-like rats maintained their brain activity at a level comparable to cocaine-naïve controls. We also evaluated brain activity during cocaine bingeing, finding a general reduction of brain activity in cocaine experienced rats independent of an addiction-like phenotype. These findings indicate that brain hypoactivity in cocaine addiction is associated with the development of compulsive use rather than the amount of cocaine consumed, and may be used as a potential biomarker for addiction that clearly distinguishes non-addict-like vs addict-like cocaine use.

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“…With both MnCl 2 administration procedures regional distribution of T1 reduction is consistent with previous research 25 , 52 .…”

Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cocaine addicted rats show reduced neural activity as revealed by manganese-enhanced MRI

Cannella

Cosa‐Linan

Takahashi

et al. 2020

Sci Rep

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“…MEMRI was performed as described previously (Perez et al, 2018; Zubcevic et al, 2018). Before the treatment, the animals used in the experiment were handled every two weeks and acclimatized to the investigator.…”

Section: Methodsmentioning

confidence: 99%

The Role of BTBD9 in Striatum and Restless Legs Syndrome

Lyu

Xiao

DeAndrade

et al. 2019

eNeuro

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Restless legs syndrome (RLS) is a sensory-motor neurological disorder characterized by uncomfortable sensations in the extremities, generally at night, which is often relieved by movements. Genome-wide association studies (GWAS) have identified mutations in BTBD9 conferring a higher risk of RLS. Knockout of the BTBD9 homolog in mice (Btbd9) and fly results in motor restlessness and sleep disruption. Clinical studies have found RLS patients have structural and functional abnormalities in the striatum; however, whether and how striatal pathology contributes to the pathogenesis of RLS is not known. Here, we used fMRI to map regions of altered synaptic activity in basal ganglia of systematic Btbd9 knock-out (KO) mice. We further dissected striatal circuits using patch-clamp electrophysiological recordings in brain slices. Two different mouse models were generated to test the effect of specific knockout of Btbd9 in either striatal medium spiny neurons (MSNs) or cholinergic interneurons (ChIs) using the electrophysiological recording, motor and sensory behavioral tests. We found that Btbd9 KO mice showed enhanced neural activity in the striatum, increased postsynaptic currents in the MSNs, and decreased excitability of the striatal ChIs. Knocking out Btbd9 specifically in the striatal MSNs, but not the ChIs, led to rest-phase specific motor restlessness, sleep disturbance, and increased thermal sensation in mice, which are consistent with results obtained from the Btbd9 KO mice. Our data establish the role of Btbd9 in regulating the activity of striatal neurons. Increased activity of the striatal MSNs, possibly through modulation by the striatal ChIs, contributes to the pathogenesis of RLS.

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“…It is noteworthy that female rats generally show increased neural activity with single cocaine exposure but reduced activity with repeated exposure, while male rats generally show a trend with opposite effects 193 . Repeated exposure of drugs could affect various brain circuits involving a number of neurotransmitters modulating reward, learning, memory, emotion, visual process and locomotion in hippocampal, amygdala and midbrain areas.…”

Section: Effects Of Estrogens On Cns Neurtransmissionmentioning

confidence: 97%

Effects of Estrogens on Central Nervous System Neurotransmission: Implications for Sex Differences in Mental Disorders

Krolick

Zhu

Shi

2018

Progress in Molecular Biology and Translational Science

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Nearly one of every five US individuals aged twelve years old or older live with certain types of mental disorders. Men are more likely to use various types of substances, while women tend to be more susceptible to mood disorders, addiction, and eating disorders, all of which are risks associated with suicidal attempts. Fundamental sex differences exist in multiple aspects of functions and activities of neurotransmitter-mediated neural circuits in the central nervous system (CNS). Dysregulation of these neural circuits would lead to various types of mental disorders. The potential mechanisms of sex differences in the CNS neural circuitry regulating mood, reward, and motivation are only beginning to be understood, although they have been largely attributed to the effects of sex hormones on CNS neurotransmission pathways. Understanding this topic is important for developing prevention and treatment of mental disorders that should be tailored differently between men and women. Studies using animal models have provided important insights into pathogenesis, mechanisms, and new therapeutic approaches of human diseases, but some concerns remain to be addressed. The purpose of this chapter is to integrate human and animal studies involving the effects of sex hormone estrogens on CNS neurotransmission, reward processing, and associated mental disorders. We provide an overview of existing evidence for the physiological, behavioral, cellular and molecular actions of estrogens in the context of controlling neurotransmission in the CNS circuits regulating mood, reward and motivation, and discuss related pathology that leads to related mental disorders.

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Cocaine differentially affects synaptic activity in memory and midbrain areas of female and male rats: an in vivo MEMRI study

Cited by 13 publications

References 97 publications

Cocaine addicted rats show reduced neural activity as revealed by manganese-enhanced MRI

Cocaine addicted rats show reduced neural activity as revealed by manganese-enhanced MRI

The Role of BTBD9 in Striatum and Restless Legs Syndrome

Effects of Estrogens on Central Nervous System Neurotransmission: Implications for Sex Differences in Mental Disorders

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