Curiosity and Mesolimbic Functional Connectivity Drive Information Seeking in Real Life.

Curiosity reflects an individual's intrinsic motivation to seek information in order to close information gaps. In laboratory-based experiments, both curiosity and information seeking have been associated with enhanced neural dynamics in the mesolimbic dopaminergic circuit. However, it is unclear whether curiosity and dopaminergic dynamics drive information seeking in real life. We investigated (i) whether curiosity predicts different characteristics of real-life information seeking and (ii) whether functional connectivity within the mesolimbic dopaminergic circuit is associated with information seeking outside the laboratory. Up to 15 months before the COVID-19 pandemic, curiosity and anxiety questionnaires, and a 10-minute resting-state fMRI session were conducted. In a follow-up survey early during the COVID-19 pandemic, participants repeated the questionnaires and completed an additional questionnaire about their COVID-19-related information seeking. Individual differences in curiosity but not anxiety were positively associated with the frequency of information-seeking behaviour. Additionally, the frequency of information seeking was predicted by individual differences in resting-state functional connectivity between the ventral tegmental area and the nucleus accumbens. The present translational study paves the way for future studies on the role of curiosity in real-life information seeking by showing that both curiosity and mesolimbic dopaminergic functional network support real-life information-seeking behaviour.

Hippocampal and amygdalar increased BDNF expression in the extinction of opioid-induced place preference.

The opioid crisis was exacerbated during the COVID-19 pandemic in the United States with alarming statistics about overdose-related deaths. Current treatment options, such as medication assisted treatments, have been unable to prevent relapse in many patients, whereas cue-based exposure therapy have had mixed results in human trials. To improve patient outcomes, it is imperative to develop animal models of addiction to understand molecular mechanisms and identify potential therapeutic targets. We previously found increased brain derived neurotrophic factor (bdnf) transcript in the ventral striatum/nucleus accumbens (VS/NAc) of rats that extinguished morphine-induced place preference. Here, we expand our study to determine whether BDNF protein expression was modulated in mesolimbic brain regions of the reward system in animals exposed to extinction training. Drug conditioning and extinction sessions were followed by Western blots for BDNF in the hippocampus (HPC), amygdala (AMY) and VS/NAc. Rears, as a measure of withdrawal-induced anxiety were also measured to determine their impact on extinction. Results showed that animals who received extinction training and successfully extinguished morphine CPP significantly increased BDNF in the HPC when compared to animals deprived of extinction training (sham-extinction). This increase was not significant in animals who failed to extinguish (extinction-resistant). In AMY, all extinction-trained animals showed increased BDNF, regardless of behavior phenotype. No BDNF modulation was observed in the VS/NAc. Finally, extinction-trained animals showed no difference in rears regardless of extinction outcome, suggesting that anxiety elicited by drug withdrawal did not significantly impact extinction of morphine CPP. Our results suggest that BDNF expression in brain regions of the mesolimbic reward system could play a key role in extinction of opioid-induced maladaptive behaviors and represents a potential therapeutic target for future combined pharmacological and extinction-based therapies.

Ribosomal DNA transcription is increased in the left nucleus accumbens of heroin-dependent males.

Opioid addiction is a worldwide problem accentuated in the USA and European countries by the COVID-19 pandemic. The nucleus accumbens (NAc) plays an outstanding neurobiological role in opioid addiction as a part of the striatum and key component of brain reward system. The striatal GABAergic medium spiny projection neurons (MSNs) are the main neuronal type in the NAc where addiction-specific synaptic plasticity occurs. The activity of ribosomal DNA (rDNA) transcription is crucial for neural plasticity and molecular studies suggest its increase in the NAc of heroin addicts. Silver-stained argyrophilic nucleolar organizer region (AgNOR) areas visualised in neuronal nuclei in paraffin-embedded brain sections are reliable morphological estimators of rDNA transcription and thus surrogate markers for the activity of brain regions. Our study revealed increased AgNOR areas in MSNs of the left NAc in 11 heroin addicts versus 11 healthy controls from the Magdeburg Brain Bank (U-test P = 0.007). No differences were observed in another investigated part of the striatum, namely the head of caudate nucleus, which is located closely to the NAc. The results were not confounded by significant differences in the age, brain volume and time of formalin fixation existing between compared groups. Our findings suggest an increased NAc activity in heroin addicts, which is consistent with human and animal experimental data.

Proposing a “Brain Health Checkup (BHC)” as a Global Potential “Standard of Care” to Overcome Reward Dysregulation in Primary Care Medicine: Coupling Genetic Risk Testing and Induction of “Dopamine Homeostasis”

In 2021, over 100,000 people died prematurely from opioid overdoses. Neuropsychiatric and cognitive impairments are underreported comorbidities of reward dysregulation due to genetic antecedents and epigenetic insults. Recent genome-wide association studies involving millions of subjects revealed frequent comorbidity with substance use disorder (SUD) in a sizeable meta-analysis of depression. It found significant associations with the expression of NEGR1 in the hypothalamus and DRD2 in the nucleus accumbens, among others. However, despite the rise in SUD and neuropsychiatric illness, there are currently no standard objective brain assessments being performed on a routine basis. The rationale for encouraging a standard objective Brain Health Check (BHC) is to have extensive data available to treat clinical syndromes in psychiatric patients. The BHC would consist of a group of reliable, accurate, cost-effective, objective assessments involving the following domains: Memory, Attention, Neuropsychiatry, and Neurological Imaging. Utilizing primarily PUBMED, over 36 years of virtually all the computerized and written-based assessments of Memory, Attention, Psychiatric, and Neurological imaging were reviewed, and the following assessments are recommended for use in the BHC: Central Nervous System Vital Signs (Memory), Test of Variables of Attention (Attention), Millon Clinical Multiaxial Inventory III (Neuropsychiatric), and Quantitative Electroencephalogram/P300/Evoked Potential (Neurological Imaging). Finally, we suggest continuing research into incorporating a new standard BHC coupled with qEEG/P300/Evoked Potentials and genetically guided precision induction of “dopamine homeostasis” to diagnose and treat reward dysregulation to prevent the consequences of dopamine dysregulation from being epigenetically passed on to generations of our children.