Decreased consumption of natural rewards in rhesus monkeys with prolonged methamphetamine abstinence.

Rationale: Relapse to drug use is a major clinical challenge in the treatment of addictive disorders, including psychostimulant use and may be exacerbated by reduced sensitivity to natural, non-drug reward. Given the relatively limited set of outcomes, and short withdrawal time in rodent studies, we conducted a more detailed assessment of the response to natural rewards in methamphetamine (METH) naive versus exposed monkeys during long-term abstinence.

Methods: This study introduced an improved sucrose preference test (iSPT) to assess natural reward seeking and consumption in monkeys with long-term abstinence after methamphetamine (METH) use.

A 3D-Printed helmet for precise and repeatable neuromodulation targeting in awake non-human primates.

The application of non-invasive brain stimulation (NIBS) in non-human primates (NHPs) is critical for advancing understanding of brain networks and developing treatments for neurological diseases. Improving the precision of targeting can significantly enhance the efficacy of these interventions. Here, we introduce a 3D-printed helmet designed to achieve repeatable and precise neuromodulation targeting in awake rhesus monkeys, eliminating the need of head fixation.

Characterization of Gut Microbiota in Rats and Rhesus Monkeys After Methamphetamine Self-administration.

Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models.

Rhesus monkeys exhibiting spontaneous ritualistic behaviors resembling obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric disorder that affects ∼2%-3% of the population globally. Studying spontaneous OCD-like behaviors in non-human primates may improve our understanding of the disorder. In large rhesus monkey colonies, we found 10 monkeys spontaneously exhibiting persistent sequential motor behaviors (SMBs) in individual-specific sequences that were repetitive, time-consuming and stable over prolonged periods.

Repeated methamphetamine exposure decreases plasma brain-derived neurotrophic factor levels in rhesus monkeys.

Background: Brain-derived neurotrophic factor (BDNF) is known to prevent methamphetamine (METH)-induced neurotoxicity and plays a role in various stages of METH addiction. However, there is a lack of research with longitudinal design on changes in plasma BDNF levels in active METH-dependent individuals.

Aims: The aim of the study was to investigate changes in BDNF levels during METH self-administration in monkeys.

Alzheimer's Disease-Like Pathologies and Cognitive Impairments Induced by Formaldehyde in Non-Human Primates.

Background: Formaldehyde (FA) has been implicated in Alzheimer's disease (AD) pathology as an age-related factor and as a protein cross-linker known to aggregate Amyloid-Beta (Aβ) and tau protein in vitro. Higher levels of FA have also been found in patients with greater cognitive impairment and in AD patient brains.

Objective: To directly evaluate the effect of chronically elevated FA levels on the primate brain with respect to AD pathological markers.

The caudal part of the posterior insula of rats participates in the maintenance but not the acquisition of morphine conditioned place preference.

The heterogeneous insular cortex plays an interoceptive role in drug addiction by signaling the availability of drugs of abuse. Here, we tested whether the caudal part of the multisensory posterior insula (PI) stores somatosensory-associated rewarding memories. Using Sprague Dawley rats as subjects, we first established a morphine-induced conditioned place preference (CPP) paradigm, mainly based on somatic cues.

Neurons Differentiated from Transplanted Stem Cells Respond Functionally to Acoustic Stimuli in the Awake Monkey Brain.

Here, we examine whether neurons differentiated from transplanted stem cells can integrate into the host neural network and function in awake animals, a goal of transplanted stem cell therapy in the brain. We have developed a technique in which a small "hole" is created in the inferior colliculus (IC) of rhesus monkeys, then stem cells are transplanted in situ to allow for investigation of their integration into the auditory neural network. We found that some transplanted cells differentiated into mature neurons and formed synaptic input/output connections with the host neurons.

Evidence for Conversion of Methanol to Formaldehyde in Nonhuman Primate Brain.

Many studies have reported that methanol toxicity to primates is mainly associated with its metabolites, formaldehyde (FA) and formic acid. While methanol metabolism and toxicology have been best studied in peripheral organs, little study has focused on the brain and no study has reported experimental evidence that demonstrates transformation of methanol into FA in the primate brain. In this study, three rhesus macaques were given a single intracerebroventricular injection of methanol to investigate whether a metabolic process of methanol to FA occurs in nonhuman primate brain.

Alzheimer's disease and methanol toxicity (part 2): lessons from four rhesus macaques (Macaca mulatta) chronically fed methanol.

A recently established link between formaldehyde, a methanol metabolite, and Alzheimer's disease (AD) pathology has provided a new impetus to investigate the chronic effects of methanol exposure. This paper expands this investigation to the non-human primate, rhesus macaque, through the chronic feeding of young male monkeys with 3% methanol ad libitum. Variable Spatial Delay Response Tasks of the monkeys found that the methanol feeding led to persistent memory decline in the monkeys that lasted 6 months beyond the feeding regimen.

Alzheimer's disease and methanol toxicity (part 1): chronic methanol feeding led to memory impairments and tau hyperphosphorylation in mice.

Although methanol toxicity is well known for acute neurological sequelae leading to blindness or death, there is a new impetus to investigate the chronic effects of methanol exposure. These include a recently established link between formaldehyde, a methanol metabolite, and Alzheimer's disease (AD) pathology. In the present study, mice were fed with methanol to revisit the chronic effects of methanol toxicity, especially as it pertains to AD progression.

Epidemiological and histopathological study of relevance of Guizhou Maotai liquor and liver diseases.

Aim: To explore the relevance of Maotai liquor and liver diseases.

Methods: Epidemiological study was conducted on groups of subjects, each consisting of 3 subjects from the Maotai liquor group consisting of 99 individuals and one from the non-alcoholic control group consisting of 33 individuals. Liver biopsy was performed on 23 volunteers from Guizhou Maotai Distillery who had a constant and long history of drinking Maotai liquor.