People who use methamphetamine evaluate incentives differently and make choices that lead to fewer rewards compared to controls. We sought to investigate whether reward context and corresponding neural activations exert different effects on choice behavior for people with problematic methamphetamine-use experience (MA+, n = 83) compared to methamphetamine-naïve controls (MA−, n = 98). Functional magnetic resonance imaging was acquired during an Incentive Processing Task (IPT), which manipulated monetary wins and losses leading to periods of reward abundance or scarcity. Reward context was operationalized via trial-by-trial monetary outcomes across the IPT and modeled using an exponentially-weighted moving average of reward availability (i.e., reward rate). Behavioral results showed that reward rate influenced choice consistency (i.e., repeating choices or not) for both groups, but losses exerted minimal influence on MA+participants’ choices regardless of reward rate. In the brain, fluctuations in reward rate were significantly and positively correlated with BOLD-signal fluctuations within striatum and frontoparietal network areas for both groups. Whole brain and ROI analyses indicated no group differences in neural tracking of reward rate. However, unlike the MA−group, this neural tracking of reward rate within dorsal striatum and frontoparietal network areas did not predict choice consistency for MA+participants. Overall, the reduced influence of prior losses for MA+participants may necessitate choice strategies less reliant on reward context. This aligns with the reduced influence of neural tacking in the MA+ group, and further suggests that losses might not be readily incorporated into working memory representations of reward context among people who use methamphetamine.
Early adulthood is a critical developmental period for the emergence of alcohol and substance use disorders (A/SUD). Young adults with family histories of A/SUD (FH+) have a higher risk for developing A/SUD themselves compared to individuals without such family histories (FH−). FH+ individuals often exhibit behavioral and cognitive alterations similar to those observed in A/SUD populations; however, A/SUD-related structural brain alterations have not been consistently observed in FH+ neuroimaging studies, which may reflect underlying heterogeneity in FH+ individuals. We compared n = 79 FH+ and 128 FH− young adults (ages 18–25) on brain volume differences in five regions of interest identified from prior A/SUD neuroimaging mega-analyses. Additionally, we compared study participants who scored low and high on a novel family history integrated phenotype (FHIP) score that combined family history with key phenotypic variables related to FH+ status. FH+ participants displayed trend-level reductions in corpus callosum volumes compared to FH− participants. However, participants with high FHIP scores had significantly decreased whole corpus callosum and increased amygdala volumes compared to participants with low FHIP scores. Post hoc testing of corpus callosum subregions found that participants with high FHIP scores had significantly reduced mid-anterior corpus callosum volume. There were no differences in hippocampus, thalamus, or putamen volumes between FH or FHIP score-based groupings. FHIP scores were more sensitive than family history status alone in identifying structural brain differences in non-abusing healthy young adults. These findings suggest that corpus callosum and amygdala volumes differences could be related to a possible overarching A/SUD-relevant endophenotype rather than simply be consequences of problem alcohol and other substance use.
Opioid use disorder (OUD) remains a significant public health problem across the United States, with current treatment options failing to reduce relapse rates and opioid-related mortality. Hyperbaric oxygen treatment (HBOT) is a non-pharmacological intervention that has been shown to alleviate opioid withdrawal symptoms in small clinical and preclinical studies. However, no clinical or preclinical research to date has examined the effects of HBOT on opioid seeking. Using a long-access (LgA) heroin self-administration rodent model (6 h/day), we found that a single 1-hour HBOT session, administered 24 h after the last of 12 daily self-administration sessions, reduced cued responding following 14 days of forced abstinence in female, but not in male rats. This study demonstrates that HBOT attenuates heroin seeking in a translationally relevant preclinical model and provides a platform for future optimization of HBOT parameters, mechanistic investigation, and evaluation of its therapeutic potential for OUD.
Maladaptive consummatory behaviors can arise from dysregulated circuits, like those in the extended amygdala, governing motivation and feeding behaviors. Neurotensin (NTS), expressed throughout the central, peripheral, and enteric nervous systems, has well-established roles in energy balance and feeding. SBI-553, a biased allosteric modulator of NTSR1, recruits β-arrestin while attenuating Gq-mediated signaling. We used SBI-553 to examine NTS modulation GABAergic signaling in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) and probed its effects on food consumption in mice. We found that NTS and SBI-553 differentially modulate GABAergic neurotransmission across extended amygdala subregions. In vivo, SBI-553 reduces palatable food consumption in both fed and food-deprived mice, with greater reductions under fasted conditions, altering activation across CeA subregions in a sex- and feeding-state-dependent manner. In the BNST, differences in SBI-553 altered cFos activity were observed between feeding states.
Alcohol and nicotine are two leading causes of preventable deaths in the United States. Simultaneous co-use of alcohol and nicotine is rising, as is the use of electronic nicotine delivery systems (ENDs). During early alcohol and nicotine co-use, users report decreased anxiety and increased feelings of pleasure. The prelimbic (PL) region of the medial prefrontal cortex (mPFC) is a target of alcohol- and nicotine-related plasticity. We investigated the consequences of acute, simultaneous alcohol and nicotine exposure on PL activity and anxiety-like behavior in female and male Sprague Dawley rats. We found that alcohol and nicotine alone or in combination increased PL neuron excitability in both females and males. Alcohol alone significantly decreased continuous evoked firing in females but not in males, and no changes were seen following nicotine alone or alcohol and nicotine in combination. In a separate experiment, immediately following acute alcohol/nicotine, alcohol/PGVG, or air vapor exposure, rats went through the novelty suppressed feeding assay. Though no differences were seen in latency to initiate feeding, females exposed to alcohol and nicotine spent more time in center compared to air/air and EtOH/PGVG controls and males exposed to ethanol and nicotine spent more time in center than air/air controls only. Females and males had decreased PL cFos activation following alcohol and nicotine vapor exposure compared to air/air controls. Together, these data suggest that alcohol and nicotine co-exposure differentially affect PL activity and anxiety-like behavior, potentially contributing to alcohol and nicotine co-use addiction pathology.
