Role of nucleus accumbens core but not shell in incubation of methamphetamine craving after voluntary abstinence

We recently introduced an animal model to study incubation of drug craving after prolonged voluntary abstinence, mimicking the human condition of relapse after successful contingency management treatment. Here we studied the role of the nucleus accumbens (NAc) in this model. We trained rats to self-administer a palatable solution (sucrose+maltodextrin 1%, 6 h/day, 6 days) and methamphetamine (6 h/day, 12 days). We then evaluated relapse to methamphetamine seeking after 1 and 15 days of voluntary abstinence, achieved via a discrete choice procedure between the palatable solution and methamphetamine (14 days). We used RNAscope in-situ hybridization to quantify the co-labeling of the neuronal activity marker Fos, and dopamine Drd1- and Drd2-expressing medium spiny neurons (MSNs) in NAc core and shell during the incubation tests. Next, we determined the effect of pharmacological inactivation of NAc core and shell by either GABAA and GABAB agonists (muscimol+baclofen, 50+50 ng/side), Drd1-Drd2 antagonist (flupenthixol, 10 µg/side) or the selective Drd1 or Drd2 antagonists (SCH39166 1.0 µg/side or raclopride 1.0 µg/side) during the relapse tests. Incubated methamphetamine seeking after voluntary abstinence was associated with a selective increase of Fos expression in the NAc core, but not shell, and Fos was co-labeled with both Drd1- and Drd2-MSNs. NAc core, but not shell, injections of muscimol+baclofen, flupenthixol, SCH39166, and raclopride reduced methamphetamine seeking after 15 days of abstinence. Together, our results suggest that dopamine transmission through Drd1 and Drd2 in NAc core is critical to the incubation of methamphetamine craving after voluntary abstinence

Long-Term Evolution of Malnutrition and Loss of Muscle Strength after COVID-19: A Major and Neglected Component of Long COVID-19

Post-acute consequences of COVID-19, also termed long COVID, include signs and symptoms persisting for more than 12 weeks with prolonged multisystem involvement; most often, however, malnutrition is ignored. Method: The objective was to analyze persistent symptoms, nutritional status, the evolution of muscle strength and performance status (PS) at 6 months post-discharge in a cohort of COVID-19 survivors. Results: Of 549 consecutive patients hospitalized for COVID-19 between 1 March and 29 April 2020, 23.7% died and 288 patients were at home at D30 post-discharge. At this date, 136 of them (47.2%) presented persistent malnutrition, a significant decrease in muscle strength or a PS ≥ 2. These patients received dietary counseling, nutritional supplementation, adapted physical activity guidance or physiotherapy assistance, or were admitted to post-care facilities. At 6 months post-discharge, 91.0% of the 136 patients (n = 119) were evaluated and 36.0% had persistent malnutrition, 14.3% complained of a significant decrease in muscle strength and 14.9% had a performance status > 2. Obesity was more frequent in patients with impairment than in those without (52.8% vs. 31.0%; p = 0.0071), with these patients being admitted more frequently to ICUs (50.9% vs. 31.3%; p = 0.010). Among those with persistent symptoms, 10% had psychiatric co-morbidities (mood disorders, anxiety, or post-traumatic stress syndrome), 7.6% had prolonged pneumological symptoms and 4.2% had neurological symptoms. Conclusions: Obese subjects as well as patients who have stayed in intensive care have a higher risk of functional loss or undernutrition 6 months after a severe COVID infection. Malnutrition and loss of muscle strength should be considered in the clinical assessment of these patients

Multiple endocrine neoplasia type 1 caused by mosaic mutation: clinical follow-up and genetic counseling?

International audienceMEN1 is an autosomal dominant hereditary syndrome characterized by several endocrine tumors, in most cases affecting the parathyroid glands, pancreas, and anterior pituitary. It is the result of inactivating mutations in the tumor suppressor gene MEN1. More than 1300 different mutations have been identified in this gene. Mosaic MEN1 mutations have been previously described in only a few patients in the literature. In this paper, we provide a review of six cases of MEN1 mosaicism reported in the literature supplemented with six additional cases described by the French TENgen network of laboratories. This review highlights that (i) MEN1 mosaicism is not associated with a mild phenotype and results in the same natural history as heterozygous MEN1 mutation and (ii) that more systematic detection of MEN1 mosaic mutation enables improvements in both patient monitoring and genetic counseling