scholarly journals Prelimbic cortex is a common brain area activated during cue-induced reinstatement of cocaine and heroin seeking in a polydrug self-administration rat model

2018 ◽  
Vol 49 (2) ◽  
pp. 165-178 ◽  
Author(s):  
Francisco J. Rubio ◽  
Richard Quintana-Feliciano ◽  
Brandon L. Warren ◽  
Xuan Li ◽  
Kailyn F. R. Witonsky ◽  
...  
Keyword(s):  
Rat Model ◽  
Brain Area ◽  
Prelimbic Cortex ◽  
Self Administration

scholarly journals Restoration of Kv7 channel mediated inhibition reduces cued-reinstatement of cocaine seeking

2018 ◽  
Author(s):  
Jeffrey Parrilla-Carrero ◽  
William C. Buchta ◽  
Priyodarshan Goswamee ◽  
Oliver Culver ◽  
Greer McKendrick ◽  
...  
Keyword(s):  
Rat Model ◽  
Prelimbic Cortex ◽  
Spike Frequency Adaptation ◽  
Self Administration ◽  
Cellular Mechanisms ◽  
Drug Seeking ◽  
Kv7 Channels ◽  
Channel Function ◽  
Cocaine Seeking ◽  
Seeking Behavior

AbstractCocaine addicts display increased sensitivity to drug-associated cues, due in part to pathological changes in the prelimbic cortex (PL-PFC). The cellular mechanisms underlying cue-induced reinstatement of cocaine seeking remain unknown. Reinforcement learning for addictive drugs may produce persistent maladaptations in intrinsic excitability within sparse subsets of PFC pyramidal neurons. Using a male rat model of relapse to cocaine-seeking, we sampled over 600 neurons to examine spike frequency adaptation (SFA) and after-hyperpolarizations (AHPs), two systems that attenuate low frequency inputs to regulate neuronal synchronization. We observed that training to self-administer cocaine or nondrug (sucrose) reinforcers decreased SFA and AHPs in a sub-population of PL-PFC neurons, but only with cocaine did the resulting hyper-excitability persist through extinction training and increase during reinstatement. In neurons with intact SFA, dopamine enhanced excitability by inhibiting Kv7 potassium channels that mediate SFA. However, dopamine effects were occluded in neurons from cocaine-experienced rats, where SFA and AHPs were reduced. Pharmacological stabilization of Kv7 channels with retigabine restored SFA and Kv7 channel function in neuroadapted cells. When microinjected bilaterally into the PL-PFC 10 minutes prior to reinstatement testing, retigabine reduced cue-induced reinstatement of cocaine seeking. Lastly, using cFos-GFP transgenic rats, we found that the loss of SFA correlated with the expression of cFos-GFP following both extinction and re-exposure to drug-associated cues. Taken together, these data suggest that cocaine self-administration desensitizes inhibitory Kv7 channels in a subpopulation of PL-PFC neurons. This sub-population of neurons may represent a persistent neural ensemble responsible for driving drug seeking in response to cues.Significance StatementLong after the cessation of drug use, cues associated with cocaine still elicit drug-seeking behavior, in part by activation of the prelimbic cortex (PL-PFC). The underlying cellular mechanisms governing these activated neurons remain unclear. Using a rat model of relapse to cocaine seeking, we identified a population of PL-PFC neurons that become hyperexcitable following chronic cocaine self-administration. These neurons show persistent loss of spike frequency adaptation, reduced after-hyperpolarizations, decreased sensitivity to dopamine, and reduced Kv7 channel mediated inhibition. Stabilization of Kv7 channel function with retigabine normalized neuronal excitability, restored Kv7 channel currents, and reduced drug-seeking behavior when administered into the PL-PFC prior to reinstatement. These data highlight a persistent adaptation in a subset of PL-PFC neurons that may contribute to relapse vulnerability.

Using anticipatory and drug-evoked appetitive ultrasonic vocalization for monitoring the rewarding effect of amphetamine in a rat model of drug self-administration

2019 ◽  
Vol 376 ◽  
pp. 112187 ◽  
Author(s):  
Karolina Kuchniak ◽  
Edyta Wyszogrodzka ◽  
Stanisław J. Chrapusta ◽  
Magdalena Czarna ◽  
Magdalena Michalak ◽  
...  
Keyword(s):  
Rat Model ◽  
Ultrasonic Vocalization ◽  
Self Administration ◽  
Rewarding Effect

scholarly journals Homeostatic state of microglia in a rat model of chronic sleep restriction

SLEEP ◽  
2020 ◽  
Vol 43 (11) ◽  
Author(s):  
Shannon Hall ◽  
Samüel Deurveilher ◽  
George S Robertson ◽  
Kazue Semba
Keyword(s):  
Rat Model ◽  
Inflammatory Cytokine ◽  
Male Rats ◽  
Sleep Restriction ◽  
Mrna Levels ◽  
Prelimbic Cortex ◽  
Adaptive Responses ◽  
Brain Functions ◽  
Anti Inflammatory ◽  
Chronic Sleep

Abstract Chronic sleep restriction (CSR) negatively impacts brain functions. Whether microglia, the brain’s resident immune cells, play any role is unknown. We studied microglia responses to CSR using a rat model featuring slowly rotating wheels (3 h on/1 h off), which was previously shown to induce both homeostatic and adaptive responses in sleep and attention. Adult male rats were sleep restricted for 27 or 99 h. Control rats were housed in locked wheels. After 27 and/or 99 h of CSR, the number of cells immunoreactive for the microglia marker ionized calcium-binding adaptor molecule-1 (Iba1) and the density of Iba1 immunoreactivity were increased in 4/10 brain regions involved in sleep/wake regulation and cognition, including the prelimbic cortex, central amygdala, perifornical lateral hypothalamic area, and dorsal raphe nucleus. CSR neither induced mitosis in microglia (assessed with bromodeoxyuridine) nor impaired blood–brain barrier permeability (assessed with Evans Blue). Microglia appeared ramified in all treatment groups and, when examined quantitatively in the prelimbic cortex, their morphology was not affected by CSR. After 27 h, but not 99 h, of CSR, mRNA levels of the anti-inflammatory cytokine interleukin-10 were increased in the frontal cortex. Pro-inflammatory cytokine mRNA levels (tumor necrosis factor-α, interleukin-1β, and interleukin-6) were unchanged. Furthermore, cortical microglia were not immunoreactive for several pro- and anti-inflammatory markers tested, but were immunoreactive for the purinergic P2Y12 receptor. These results suggest that microglia respond to CSR while remaining in a physiological state and may contribute to the previously reported homeostatic and adaptive responses to CSR.

Intravenous self-administration of amphetamine is increased in a rat model of depression

Synapse ◽  
2002 ◽  
Vol 46 (1) ◽  
pp. 4-10 ◽  
Author(s):  
Philip V. Holmes ◽  
Cher V. Masini ◽  
Stefany D. Primeaux ◽  
Joshua L. Garrett ◽  
Andrew Zellner ◽  
...  
Keyword(s):  
Rat Model ◽  
Self Administration

2Hz-Electroacupuncture Attenuates Conditioned Cue-Evoked Heroin-Seeking Behavior and Increase CB2-Rs Expression in Relapse-Relevant Brain Regions in Heroin-Addicted Rats

2014 ◽  
Vol 998-999 ◽  
pp. 164-168 ◽  
Author(s):  
Lin Chen ◽  
Bao Miao Ma ◽  
Kai Yue ◽  
Qin Ru ◽  
Xiang Tian ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Rat Model ◽  
Fixed Ratio ◽  
Brain Regions ◽  
Inhibitory Effect ◽  
Control Group ◽  
Self Administration ◽  
Seeking Behavior

In order to investigate the influence of electroacupuncture on heroin seeking behavior and the expression of CB2-Rs in the relapse-relevant brain regions, heroin self-administration rat model which represents the heroin relapse behaviors was developed with progressive fixed ratio program. The model rats were randomly divided into 3 groups: control group, heroin-addicted group and 2Hz electroacupuncture group (stimulating on acupoints zusanli and sanyinjiao). The expression of CB2-Rs in the relapse-relevant brain regions were assessed with immunohistochemistry technologies. The reinstatement of heroin seeking behavior induced by conditioned cue priming showed that compared with the heroin-addicted group, active pokes in the 2Hz electroacupuncture group decreased significantly (p<0.05). Compared with the control group, the expression of CB2-Rs in prefrontal cortex (PFC) and nucleus accumbens (NAc) was significantly decreased (p<0.05) in heroin-addicted group and increaseed significantly recover (p<0.05) in the 2Hz electroacupuncture group. Our present results showed that 2Hz-electroacupuncture could attenuate the conditioned cue-evoked heroin-seeking behavior and the inhibitory effect was mediated partially by the increase CB2-Rs expression in relapse-relevant brain regions in heroin-addicted rats.

Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia

2017 ◽  
Vol 32 (1) ◽  
pp. 121-133 ◽  
Author(s):  
Jana Ruda-Kucerova ◽  
Zuzana Babinska ◽  
Tibor Stark ◽  
Vincenzo Micale
Keyword(s):  
Rat Model ◽  
Self Administration ◽  
Pre Treatment

scholarly journals Allosteric modulation of GABAA receptors in rat basolateral amygdala blocks stress-enhanced reacquisition of nicotine self-administration

2020 ◽  
Author(s):  
Burt M Sharp ◽  
Qin Jiang ◽  
Xenia Simone ◽  
Petra Scholze
Keyword(s):  
Rat Model ◽  
Gabaa Receptors ◽  
Basolateral Amygdala ◽  
Allosteric Modulation ◽  
Gabaergic Interneurons ◽  
Allosteric Modulators ◽  
Self Administration ◽  
Repeated Stress ◽  
Output Neurons ◽  
Inhibitory Regulation

AbstractStress is a major determinant of relapse to smoked tobacco. In a rat model, repeated stress during abstinence from nicotine self-administration (SA) results in enhanced reacquisition of nicotine SA, which is dependent on the basolateral amygdala (BLA). We postulate that repeated stress during abstinence causes hyperexcitability of BLA principal output neurons (PN) due to disinhibition of PN from reduced inhibitory regulation by local GABAergic interneurons. To determine if enhanced GABAergic regulation of BLA PNs can lessen the effects of stress on nicotine intake, positive allosteric modulators (PAMs) of GABAA receptors were infused into the BLA immediately prior to reacquisition of nicotine SA. Three selective PAMs (e.g., NS 16085, DCUK-OEt, DS2) with varied GABAA subunit specificities abolished the stress-induced amplification of nicotine taking during reacquisition. These studies indicate that highly selective PAMS targeting α3 or δ subunit-containing GABAA in BLA may be effective in ameliorating the stress-induced relapse to smoked tobacco during abstinence from cigarettes.

Prelimbic Cortex Deep Brain Stimulation Reduces Binge Size in a Chronic Binge Eating Rat Model

2018 ◽  
Vol 96 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Can Sarica ◽  
Mazhar Ozkan ◽  
Husniye Hacioglu Bay ◽  
Umit Sehirli ◽  
Filiz Onat ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Binge Eating ◽  
Brain Stimulation ◽  
Rat Model ◽  
Prelimbic Cortex ◽  
Deep Brain
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