scholarly journals Electroacupuncture Suppresses Discrete Cue-Evoked Heroin-Seeking and Fos Protein Expression in the Nucleus Accumbens Core in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Sheng Liu ◽  
Fenglei Zhu ◽  
Miaojun Lai ◽  
Limin Sun ◽  
Yijun Liu ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Therapeutic Benefit ◽  
Sprague Dawley ◽  
Contextual Cues ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Beneficial Effects ◽  
Fos Protein ◽  
Sprague Dawley Rats ◽  
Seeking Behavior

Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14 days during heroin abstinence. We tested these animals for contextual and discrete cue-induced reinstatement of active responses. We also applied immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens (NACc) core and shell after reinstatement test. We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls. EA treatment significantly reduced active responses elicited by discrete cues. EA stimulation attenuated Fos expression in the core but not the shell of the NACc. Altogether, these results highlight the therapeutic benefit of EA in preventing relapse to drug addiction.

scholarly journals Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats

2010 ◽  
Vol 104 (2) ◽  
pp. 922-931 ◽  
Author(s):  
Nii A. Addy ◽  
David P. Daberkow ◽  
Jeremy N. Ford ◽  
Paul A. Garris ◽  
R. Mark Wightman
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Cocaine Exposure ◽  
Sprague Dawley ◽  
Nucleus Accumbens Core ◽  
Fast Scan Cyclic Voltammetry ◽  
Uptake Inhibition ◽  
Sprague Dawley Rats ◽  
Dopamine Signaling

Repeated cocaine exposure and withdrawal leads to long-term changes, including behavioral and dopamine sensitization to an acute cocaine challenge, that are most pronounced after long withdrawal periods. However, the changes in dopamine neurotransmission after short withdrawal periods are less well defined. To study dopamine neurotransmission after 1-day withdrawal, we used fast-scan cyclic voltammetry (FSCV) to determine whether repeated cocaine alters rapid dopamine release and uptake in the nucleus accumbens (NAc) core and shell. FSCV was performed in urethane anesthetized male Sprague-Dawley rats that had previously received one or seven daily injections of saline or cocaine (15 mg/kg, ip). In response to acute cocaine, subjects showed increased dopamine overflow that resulted from both increased dopamine release and slowed dopamine uptake. One-day cocaine pre-exposure, however, did not alter dopaminergic responses to a subsequent cocaine challenge. In contrast, 7-day cocaine-treated subjects showed a potentiated rapid dopamine response in both the core and shell after an acute cocaine challenge. In addition, kinetic analysis during the cocaine challenge showed a greater increase in apparent Km of 7-day cocaine exposed subjects. Together, the data provide the first in vivo demonstration of rapid dopamine sensitization in the NAc core and shell after a short withdrawal period. In addition, the data clearly delineate cocaine's release and uptake effects and suggest that the observed sensitization results from greater uptake inhibition in cocaine pre-exposed subjects.

scholarly journals A subset of nucleus accumbens neurons receiving dense and functional prelimbic cortical input are required for cocaine seeking

2021 ◽  
Author(s):  
Benjamin M. Siemsen ◽  
Sarah M. Barry ◽  
Kelsey Vollmer ◽  
Lisa M. Green ◽  
Ashley G. Brock ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Glutamate Release ◽  
Sprague Dawley ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Cortical Input ◽  
Cortical Projections ◽  
Cocaine Seeking ◽  
Accumbens Core

AbstractBackgroundPrelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown.MethodsMale Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, in vivo electrochemistry, and high-resolution confocal microscopy were used to identify and characterize a small population of nucleus accumbens core neurons that receive dense prelimbic cortical input to determine their role in regulating cue-induced cocaine and natural reward seeking.ResultsChemogenetic inhibition of prelimbic cortical projections to the nucleus accumbens core suppressed cue-induced cocaine relapse and normalized real-time cue-evoked increases in accumbens glutamate release to that of sucrose seeking animals. Furthermore, chemogenetic inhibition of the population of nucleus accumbens core neurons receiving the densest prelimbic cortical input suppressed cocaine, but not sucrose seeking. These neurons also underwent morphological plasticity during the peak of cocaine seeking in the form of dendritic spine expansion and increased ensheathment by astroglial processes at large spines.ConclusionsWe identified and characterized a unique subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. The functional specificity of this subpopulation is underscored by their ability to mediate cue-induced cocaine relapse, but not sucrose seeking. This subset of cells represents a novel target for addiction therapeutics revealed by anterograde targeting to interrogate functional circuits imbedded within a known network.

scholarly journals Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

2019 ◽  
Author(s):  
Timothy G. Freels ◽  
Lydia N. Baxter-Potter ◽  
Janelle M. Lugo ◽  
Nicholas C. Glodosky ◽  
Hayden R. Wright ◽  
...  
Keyword(s):  
Fixed Ratio ◽  
Progressive Ratio ◽  
Sprague Dawley ◽  
Self Administration ◽  
Daily Food ◽  
Sprague Dawley Rats ◽  
Seeking Behavior ◽  
Break Points ◽  
Bona Fide ◽  
Novel Method

ABSTRACTRecent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug employed and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized Δ9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) complete cannabis extracts. Male Sprague Dawley rats were trained to nosepoke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily one-hour sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared to CANCBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CANTHC administration decreased hippocampal CB1 receptor binding. Removal of CANTHC reinforcement (but not CANCBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors.

scholarly journals Role of GABRD Gene Methylation in the Nucleus Accumbens in Heroin-Seeking Behavior in Rats

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingxiao Hong ◽  
Wenjin Xu ◽  
Zi Lin ◽  
Jing Liu ◽  
Weisheng Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Nucleus Accumbens ◽  
Dna Methyltransferase ◽  
Opposite Effect ◽  
Heroin Addiction ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
Self Administration ◽  
Drug Induced ◽  
Seeking Behavior

Epigenetic modifications such as DNA methylation play important roles in regulating gene expression and may mediate neuroplasticity and lead to drug-induced aberrant behaviors. Although several brain regions and neurobiological mechanisms have been suggested to be involved in these processes, there is remarkably little known about the effects of DNA methylation on heroin-seeking behavior. Using a Sprague-Dawley rat model, we show that heroin self-administration resulted in gamma-aminobutyric acid type A receptor subunit delta (GABRD) gene hypomethylation, which was associated with transcriptional upregulation of GABRD in the nucleus accumbens (NAc). Systemic l-methionine (MET) administration significantly strengthened the reinstatement of heroin-seeking behavior induced by heroin priming, whereas intra-NAc injections of the DNA methyltransferase (DNMT) inhibitor 5-aza-2′-deoxycytidine (5-Aza-dC) had the opposite effect on heroin-seeking. Meanwhile, 5-Aza-dC treatment decreased DNA methylation and upregulated the expression of GABRD in the NAc, whereas MET had the opposite effect. Our results also reveal that 5-Aza-dC might alter the methylation landscape of the GABRD gene by directly repressing DNMT1 and DNMT3A expression. Furthermore, reinstatement of heroin-seeking behavior was significantly inhibited by directly overexpressing GABRD and remarkably reinforced by GABRD gene silencing in the NAc. Collectively, these results suggest that targeting the GABRD gene and its methylation might represent a novel pharmacological strategy for treating heroin addiction and relapse.

scholarly journals Investigating the cumulative effects of Δ9-tetrahydrocannabinol and repetitive mild traumatic brain injury on adolescent rats

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Dhyey Bhatt ◽  
Ali Hazari ◽  
Glenn R Yamakawa ◽  
Sabrina Salberg ◽  
Marissa Sgro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Prefrontal Cortex ◽  
Brain Injury ◽  
Nucleus Accumbens ◽  
Mild Traumatic Brain Injury ◽  
Brain Injuries ◽  
Therapeutic Benefit ◽  
Sprague Dawley ◽  
Post Injury ◽  
Beneficial Effects

Abstract The prevalence of mild traumatic brain injury is highest amongst the adolescent population and can lead to complications including neuroinflammation and excitotoxicity. Also pervasive in adolescents is recreational cannabis use. Δ9-Tetrahydrocannabinol, the main psychoactive component of cannabis, is known to have anti-inflammatory properties and serves as a neuroprotective agent against excitotoxicity. Thus, we investigated the effects of Δ9-tetrahydrocannabinol on recovery when administered either prior to or following repeated mild brain injuries. Male and female Sprague-Dawley rats were randomly assigned to receive Δ9-tetrahydrocannabinol or vehicle either prior to or following the repeated injuries. Rats were then tested on a behavioural test battery designed to measure post-concussive symptomology. The hippocampus, nucleus accumbens and prefrontal cortex were extracted from all animals to examine mRNA expression changes (Bdnf, Cnr1, Comt, GR, Iba-1 and Vegf-2R). We hypothesized that, in both experiments, Δ9-tetrahydrocannabinol administration would provide neuroprotection against mild injury outcomes and confer therapeutic benefit. Δ9-Tetrahydrocannabinol administration following repeated mild traumatic brain injury was beneficial to three of the six behavioural outcomes affected by injury (reducing anxiety and depressive-like behaviours while also mitigating injury-induced deficits in short-term working memory). Δ9-Tetrahydrocannabinol administration following injury also showed beneficial effects on the expression of Cnr1, Comt and Vegf-2R in the hippocampus, nucleus accumbens and prefrontal cortex. There were no notable benefits of Δ9-tetrahydrocannabinol when administered prior to injury, suggesting that Δ9-tetrahydrocannabinol may have potential therapeutic benefit on post-concussive symptomology when administered post-injury, but not pre-injury.

scholarly journals The Adenosine A2A Receptor Activation in Nucleus Accumbens Suppress Cue-Induced Reinstatement of Propofol Self-administration in Rats

2021 ◽  
Author(s):  
Zhanglei Dong ◽  
Bingwu Huang ◽  
Chenchen Jiang ◽  
Jiangfan Chen ◽  
Han Lin ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
D2 Receptor ◽  
Fixed Ratio ◽  
Receptor Activation ◽  
Addictive Behaviors ◽  
Self Administration ◽  
A2a Receptors ◽  
Mediated Effects ◽  
Seeking Behavior ◽  
Adenosine A2a

AbstractPropofol has shown strong addictive properties in rats and humans. Adenosine A2A receptors (A2AR) in the nucleus accumbens (NAc) modulate dopamine signal and addictive behaviors such as cocaine- and amphetamine-induced self-administration. However, whether A2AR can modulate propofol addiction remains unknown. AAV-shA2AR was intra-NAc injected 3 weeks before the propofol self-administration training to test the impacts of NAc A2AR on establishing the self-administration model with fixed ratio 1 (FR1) schedule. Thereafter, the rats were withdrawal from propofol for 14 days and tested cue-induced reinstatement of propofol seeking behavior on day 15. The propofol withdrawal rats received one of the doses of CGS21680 (A2AR agonist, 2.5–10.0 ng/site), MSX-3 (A2AR antagonist, 5.0–20.0 μg/site) or eticlopride (D2 receptor (D2R) antagonist, 0.75–3.0 μg/site) or vehicle via intra-NAc injection before relapse behavior test. The numbers of active and inactive nose-poke response were recorded. Focal knockdown A2AR by shA2AR did not affect the acquisition of propofol self-administration behavior, but enhance cue-induced reinstatement of propofol self-administration compared with the AAV-shCTRLgroup. Pharmacological activation of the A2AR by CGS21680 (≥ 5.0 ng/site) attenuated cue-induced reinstatement of propofol self-administration behavior. Similarly, pharmacological blockade of D2R by eticlopride (0.75–3.0 μg/site) attenuated propofol seeking behavior. These effects were reversed by the administration of MSX-3 (5.0–20.0 μg/site). The A2AR- and D2R-mediated effects on propofol relapse were not confounded by the learning process, and motor activity as the sucrose self-administration and locomotor activity were not affected by all the treatments. This study provides genetic and pharmacological evidence that NAc A2AR activation suppresses cue-induced propofol relapse in rats, possibly by interacting with D2R.

scholarly journals Effects of adolescent caffeine consumption on cocaine self-administration and reinstatement of cocaine seeking

2018 ◽  
Vol 33 (1) ◽  
pp. 132-144
Author(s):  
Tracey A Larson ◽  
Casey E O’Neill ◽  
Michaela P Palumbo ◽  
Ryan K Bachtell
Keyword(s):  
Dose Response ◽  
Extinction Training ◽  
Schedules Of Reinforcement ◽  
Sprague Dawley ◽  
Self Administration ◽  
Caffeine Consumption ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Cocaine Seeking ◽  
Administration Procedure

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.

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