Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking.

Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol influence the intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with homecage access to alcohol (20% v/v) and/or water immediately after the IVSA session.

Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking.

Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol would influence intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with access to either alcohol (20% v/v) and water or only water immediately after the IVSA session.

Circuit and Cell-Specific Contributions to Decision Making Involving Risk of Explicit Punishment in Male and Female Rats.

Decision making is a complex cognitive process that recruits a distributed network of brain regions, including the basolateral amygdala (BLA) and nucleus accumbens shell (NAcSh). Recent work suggests that communication between these structures, as well as activity of cells expressing dopamine (DA) D2 receptors (D2R) in the NAcSh, are necessary for some forms of decision making; however, the contributions of this circuit and cell population during decision making under risk of punishment are unknown. The current experiments addressed this question using circuit-specific and cell type-specific optogenetic approaches in rats during a decision making task involving risk of punishment.

The role of metabotropic glutamate receptors in neurobehavioral effects associated with methamphetamine use.

Metabotropic glutamate (mGlu) receptors are expressed throughout the central nervous system and act as important regulators of drug-induced neuroplasticity and behavior. Preclinical research suggests that mGlu receptors play a critical role in a spectrum of neural and behavioral consequences arising from methamphetamine (meth) exposure. However, an overview of mGlu-dependent mechanisms linked to neurochemical, synaptic, and behavioral changes produced by meth has been lacking.

Circuit and cell-specific contributions to decision making involving risk of explicit punishment in male and female rats.

Decision making is a complex cognitive process that recruits a distributed network of brain regions, including the basolateral amygdala (BLA) and nucleus accumbens shell (NAcSh). Recent work suggests that communication between these structures, as well as activity of cells expressing dopamine D2 receptors (D2R) in the NAcSh, are necessary for some forms of decision making; however, the contributions of this circuit and cell population during decision making under risk of punishment are unknown. The current experiments addressed this question using circuit- and cell type-specific optogenetic approaches in rats during a decision-making task involving risk of punishment.

The roles of rat medial prefrontal and orbitofrontal cortices in relapse to cocaine-seeking: A comparison across methods for identifying neurocircuits.

A large body of research supports the notion that regions of the rodent frontal cortex regulate reinstatement of cocaine seeking after cessation of intravenous cocaine self-administration. However, earlier studies identifying the roles of medial (mPFC) and orbital prefrontal cortices (OFC) in reinstatement relied on pharmacological inactivation methods, which indiscriminately inhibited cells within a target region. Here, we first review the anatomical borders and pathways of the rat mPFC and OFC.

Stress resilience-associated behaviors following predator scent stress are accompanied by upregulated nucleus accumbens mGlu5 transcription in female Sprague Dawley rats.

Despite the higher prevalence of post-traumatic stress disorder (PTSD) in women, the majority of preclinical research has been conducted utilizing male subjects. We have found that male rats exposed to the predator scent 2,4,5-trimethyl-3-thiazoline (TMT) show heterogenous long-term anxiety-like behavior and conditioned fear to the TMT environment. Stress-Resilient males exhibit increased mGlu5 mRNA expression in the basolateral amygdala (BLA) and prefrontal cortex (PFC).

Metabotropic Glutamate Receptor Trafficking and its Role in Drug-Induced Neurobehavioral Plasticity.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system that guides developmental and experience-dependent changes in many cellular substrates and brain circuits, through the process collectively referred to as neurobehavioral plasticity. Regulation of cell surface expression and membrane trafficking of glutamate receptors represents an important mechanism that assures optimal excitatory transmission, and at the same time, also allows for fine-tuning neuronal responses to glutamate. On the other hand, there is growing evidence implicating dysregulated glutamate receptor trafficking in the pathophysiology of several neuropsychiatric disorders.

Orbital Mapping of Semiconducting Perylenes on Cu(111).

Semiconducting O-doped polycyclic aromatic hydrocarbons constitute a class of molecules whose optoelectronic properties can be tailored by acting on the π-extension of the carbon-based frameworks and on the oxygen linkages. Although much is known about their photophysical and electrochemical properties in solution, their self-assembly interfacial behavior on solid substrates has remained unexplored so far. In this paper, we have focused our attention on the on-surface self-assembly of O-doped bi-perylene derivatives.

Extinction vs. Abstinence: A Review of the Molecular and Circuit Consequences of Different Post-Cocaine Experiences.

The intravenous cocaine self-administration model is widely used to characterize the neurobiology of cocaine seeking. When studies are aimed at understanding relapse to cocaine-seeking, a post-cocaine abstinence period is imposed, followed by "relapse" tests to assess the ability of drug-related stimuli ("primes") to evoke the resumption of the instrumental response previously made to obtain cocaine. Here, we review the literature on the impact of post-cocaine abstinence procedures on neurobiology, finding that the prelimbic and infralimbic regions of the prefrontal cortex are recruited by extinction training, and are not part of the relapse circuitry when extinction training does not occur.

Increased mGlu5 mRNA expression in BLA glutamate neurons facilitates resilience to the long-term effects of a single predator scent stress exposure.

Post-traumatic stress disorder (PTSD) develops in a subset of individuals exposed to a trauma with core features being increased anxiety and impaired fear extinction. To model the heterogeneity of PTSD behavioral responses, we exposed male Sprague-Dawley rats to predator scent stress once for 10 min and then assessed anxiety-like behavior 7 days later using the elevated plus maze and acoustic startle response. Rats displaying anxiety-like behavior in both tasks were classified as stress Susceptible, and rats exhibiting behavior no different from un-exposed Controls were classified as stress Resilient.

A Rare Case of Severe Dilated Cardiomyopathy in Early Infancy.

We report the case of a 3-month-old girl presenting with end-stage dilated cardiomyopathy and therapy-resistant cardiogenic shock. A left ventricular assist device (LVAD) Berlin Heart EXCOR was implanted, her organs recovered, and she was listed for heart transplantation. Two months later, while still on the LVAD, she was diagnosed with the rare genetic Alström syndrome.

Using rat operant delayed match-to-sample task to identify neural substrates recruited with increased working memory load.

The delayed match-to-sample task (DMS) is used to probe working memory (WM) across species. While the involvement of the PFC in this task has been established, limited information exists regarding the recruitment of broader circuitry, especially under the low- versus high-WM load. We sought to address this question by using a variable-delay operant DMS task.

Long-term Changes in the Central Amygdala Proteome in Rats with a History of Chronic Cocaine Self-administration.

The central nucleus of the amygdala (CeA) is a striatum-like structure that contains mainly inhibitory circuits controlling a repertoire of (mal)adaptive behaviors related to pain, anxiety, motivation, and addiction. Neural activity in the CeA is also necessary for the expression of persistent and robust drug seeking, also termed 'incubation of drug craving.' However, neuroadaptations within this brain region supporting incubated drug craving have not been characterized.

The role of glutamate mGlu5 and adenosine A2a receptor interactions in regulating working memory performance and persistent cocaine seeking in rats.

Cocaine use disorder (CUD) is associated with neurobehavioral deficits that are resistant to current treatments. While craving and high rates of relapse are prominent features of CUD, persistent cognitive impairments are common and linked to poorer treatment outcomes. Here we sought to develop an animal model to study post-cocaine changes in drug seeking and working memory, and to evaluate 'therapeutic' effects of combined glutamate mGlu5 and adenosine A2a receptor blockade.

Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats.

Rationale: The beta-lactam antibiotic ceftriaxone reliably attenuates the reinstatement of cocaine seeking. While the restoration of nucleus accumbens core (NA core) GLT-1 expression is necessary for ceftriaxone to attenuate reinstatement, AAV-mediated GLT-1 overexpression is not sufficient to attenuate reinstatement and does not prevent glutamate efflux during reinstatement.

Aims: Here, we test the hypothesis that ceftriaxone attenuates reinstatement through interactions with glutamate autoreceptors mGlu2 and mGlu3 in the NA core.

Primary carnitine deficiency - diagnosis after heart transplantation: better late than never!

Background: Primary carnitine deficiency due to mutations in the SLC22A5 gene is a rare but well-treatable metabolic disorder that puts patients at risk for metabolic decompensations, skeletal and cardiac myopathy and sudden cardiac death.

Results: We report on a 7-year-old boy diagnosed with primary carnitine deficiency 2 years after successful heart transplantation thanks his younger sister's having been identified via expanded newborn screening during a pilot study evaluating an extension of the German newborn screening panel.

Conclusion: As L-carnitine supplementation can prevent and mostly reverse clinical symptoms of primary carnitine deficiency, all patients with cardiomyopathy should be investigated for primary carnitine deficiency even if newborn screening results were unremarkable.

The cognitive cost of reducing relapse to cocaine-seeking with mGlu5 allosteric modulators.

Rationale: Cocaine use disorder (CUD) remains difficult to treat with no FDA-approved medications to reduce relapse. Antagonism of metabotropic glutamate receptor 5 (mGlu5) has been demonstrated to decrease cocaine-seeking but may also further compromise cognitive function in long-term cocaine users.

Objectives: Here we assessed the effect of repeated administration of negative or positive allosteric modulators (NAM or PAM) of mGlu5 on both cognitive performance and (context+cue)-primed cocaine-seeking after prolonged abstinence (≥ 45 days).

The Divergent Effects of CDPPB and Cannabidiol on Fear Extinction and Anxiety in a Predator Scent Stress Model of PTSD in Rats.

Post-traumatic stress disorder (PTSD) currently has no FDA-approved treatments that reduce symptoms in the majority of patients. The ability to extinguish fear memory associations is impaired in PTSD individuals. As such, the development of extinction-enhancing pharmacological agents to be used in combination with exposure therapies may benefit the treatment of PTSD.

Neurobiological substrates of persistent working memory deficits and cocaine-seeking in the prelimbic cortex of rats with a history of extended access to cocaine self-administration.

Cocaine use disorder (CUD) is associated with prefrontal cortex dysfunction and cognitive deficits that may contribute to persistent relapse susceptibility. As the relationship between cognitive deficits, cortical abnormalities and drug seeking is poorly understood, development of relevant animal models is of high clinical importance. Here, we used an animal model to characterize working memory and reversal learning in rats with a history of extended access cocaine self-administration and prolonged abstinence.

The effects of clavulanic acid and amoxicillin on cue-primed reinstatement of cocaine seeking.

Research using the cocaine self-administration and reinstatement animal model of relapse finds that the beta-lactam antibiotic, ceftriaxone, attenuates cocaine-primed reinstatement of cocaine seeking and upregulates two proteins that regulate glutamate release and reuptake (xCT and GLT-1, respectively) in the nucleus accumbens core (NAc). We tested three compounds with beta-lactam rings for their ability to attenuate cue-primed reinstatement and increase GLT-1 and xCT expression in the NAc and prefrontal cortex (PFC). Rats self-administered intravenous cocaine for 1 hr/day for 7 days then 6 hrs/day for 10 days.