Serotonin (5-HT) and the habenula (Hb) contribute to motivational and emotional states such as depression and drug abuse. The dorsal raphe nucleus, where 5-HT neurons originate, and the Hb are anatomically and reciprocally interconnected. Evidence exists that 5-HT influences Hb glutamatergic transmission. Using serotonin transporter knockout (SERT ) rats, which show depression-like behavior and increased cocaine intake, we investigated the effect of SERT reduction on expression of genes involved in glutamate neurotransmission under both baseline conditions as well as after short-access or long-access cocaine (ShA and LgA, respectively) intake. In cocaine-naïve animals, SERT removal led to reduced baseline Hb mRNA levels of critical determinants of glutamate transmission, such as SLC1A2, the main glutamate transporter and N-methyl-D-aspartate (Grin1, Grin2A and Grin2B) as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (Gria1 and Gria2) receptor subunits, with no changes in the scaffolding protein Dlg4. In response to ShA and LgA cocaine intake, SLC1A2 and Grin1 mRNA levels decreased in SERT rats to levels equal of those of SERT rats. Our data reveal that increased extracellular levels of 5-HT modulate glutamate neurotransmission in the Hb, serving as critical neurobiological substrate for vulnerability to cocaine addiction.
Background: Cognitive bias refers to emotional influences on cognition and provides a cognitive measure of negativity-or positivity-bias through assessment of the behavioral responses to ambiguous stimuli. Thus, under negative conditions an animal is more likely to judge ambiguous stimuli as negative, and under positive conditions as positive. The transfer of past experiences to novel but similar situations is highly adaptive, as it allows the animal to anticipate on the most likely outcome of the ambiguous cues. Methods: We conducted a systematic review to summarize the current state of evidence on cognitive bias in rodents under adverse and rewarding or supportive conditions. Results: In total 20 studies were identified, in which auditory, spatial, tactile, or visual tasks were used. Stressed rodents generally made fewer positive responses than their non-stressed conspecifics. Housing enrichment made rodents more positive in anticipation of ambiguous cues. Ethanol seeking rats generalized the ambiguous cues to sucrose and less to ethanol if sucrose was available. Amphetamine, fluoxetine, and ketamine shifted the bias toward positivity, while reboxetine elevated negative bias. Conclusion: The auditory tasks have been most extensively validated, followed by the tactile and spatial tasks, and finally the visual tasks. The tactile and spatial tasks use latency as readout, which is sensitive to confounding factors. It is yet uncertain whether spatial tasks measure cognitive bias. Across all tasks, with some exceptions, rodents exposed to stress show less positivity-bias when exposed to ambiguous cues, whereas rodents exposed to rewarding substances or treated with antidepressant drugs are biased toward reward. Considering the methodological heterogeneity and risk of bias, the present data should be interpreted with caution.
studies from other species 12,13 , we have freely released all data and the generated code.
Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows comparison with invasive or terminal procedures. To date, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. We introduce StandardRat, a consensus rat functional MRI acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired in rats from 46 centers. We developed a reproducible pipeline for the analysis of rat data acquired with diverse protocols and determined experimental and processing parameters associated with a more robust functional connectivity detection. We show that the standardized protocol enhances biologically plausible functional connectivity patterns, relative to pre-existing acquisitions. The protocol and processing pipeline described here are openly shared with the neuroimaging community to promote interoperability and cooperation towards tackling the most important challenges in neuroscience.
Background: The present meta-analysis aimed to evaluate the efficacy of various non-pharmacological interventions on comorbid emotional symptoms such as depression, anxiety, and emotional dysregulation (ED) in children and adults with ADHD. Method: Forty-four randomized controlled trials (23 studies with ADHD children and 21 studies with ADHD adults) were included. Risk of bias, heterogeneity assessment, and subgroup analyses were conducted. Results: We found that therapies targeting the relationship between children and others (i.e., parent-training [on ED and depression] and social skills training [on ED]) were efficacious in the treatment of emotional symptoms in children with ADHD at post-intervention. As for adults with ADHD, cognitive behavioral therapy was found to be effective for the improvement of emotional symptoms at both post-intervention and follow-up. Conclusion: Our findings demonstrate that the efficacy of non-pharmacological interventions varies substantially across children and adults with ADHD. These results provide important implications for the selection of non-pharmacological interventions for children with ADHD.
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