Dietary sucrose determines the regulatory activity of lithium on gene expression and lifespan in Drosophila melanogaster.

The amount of dietary sugars and the administration of lithium both impact the lifespan of the fruit fly Drosophila melanogaster. It is noteworthy that lithium is attributed with insulin-like activity as it stimulates protein kinase B/Akt and suppresses the activity of glycogen synthase kinase-3 (GSK-3). However, its interaction with dietary sugar has largely remained unexplored. Therefore, we investigated the effects of lithium supplementation on known lithium-sensitive parameters in fruit flies, such as lifespan, body composition, GSK-3 phosphorylation, and the transcriptome, while varying the dietary sugar concentration. For all these parameters, we observed that the efficacy of lithium was significantly influenced by the sucrose content in the diet. Overall, we found that lithium was most effective in enhancing longevity and altering body composition when added to a low-sucrose diet. Whole-body RNA sequencing revealed a remarkably similar transcriptional response when either increasing dietary sucrose from 1% to 10% or adding 1 mM LiCl to a 1% sucrose diet, characterized by a substantial overlap of nearly 500 differentially expressed genes. Hence, dietary sugar supply is suggested as a key factor in understanding lithium bioactivity, which could hold relevance for its therapeutic applications.

Propranolol attenuates the establishment of conditioned context aversions: differential effects compared to MK-801 in an animal model of anticipatory nausea and vomiting.

Cancer patients often experience anticipatory nausea and vomiting (ANV) due to Pavlovian conditioning. Both N-methyl-D-aspartate and beta-adrenergic receptors are known to mediate memory formation, but their role in the development of ANV remains unclear. This study used a conditioned context aversion (CCA) paradigm, an animal model for ANV, to assess whether administration of the beta-adrenergic receptor antagonist propranolol or the N-methyl-D-aspartate receptor antagonist MK-801 immediately after CCA training has an effect on the later expression of CCA in CD1 male mice. In experiment 1, three groups were injected with lithium chloride (LiCl) to induce aversion in a novel context, resulting in CCA. A control group was injected with sodium chloride (NaCl). Following conditioning, two of the LiCl-treated groups received different doses of MK-801 (0.05 or 0.2 mg/kg), while the remaining LiCl-treated and NaCl-treated groups received a second NaCl injection. In experiment 2, two groups were injected with LiCl, and one group was injected with NaCl. After conditioning, one of the LiCl-treated groups received a propranolol injection (10 mg/kg). The remaining LiCl-treated and NaCl-treated groups received NaCl injections. Water consumption was measured in all groups 72 h later within the conditioning context. Postconditioning administration of propranolol, but not MK-801, attenuated CCA, as revealed by similar levels of water consumption in animals that received LiCl and propranolol relative to NaCl-treated animals. These findings suggest that beta-adrenergic receptor activation is crucial for the development of CCA. Therefore, propranolol may represent a novel therapeutic approach for cancer patients at high risk of ANV.

Compartmental neuronal degeneration in the ventral striatum induced by status epilepticus in young rats' brain in comparison with adults.

According to experimental and clinical studies, status epilepticus (SE) causes neurodegenerative morphological changes not only in the hippocampus and other limbic structures, it also affects the thalamus and the neocortex. In addition, several studies reported atrophy, metabolic changes, and neuronal degeneration in the dorsal striatum. The literature lacks studies investigating potential neuronal damage in the ventral component of the striatopallidal complex (ventral striatum [VS] and ventral pallidum) in SE experimentations. To better understand the development of neuronal damage in the striatopallidal complex associated with SE, the detected neuronal degeneration in the compartments of the VS, namely, the nucleus accumbens (NAc) and the olfactory tubercle (OT), was analyzed. The experiments were performed on Wistar rats at age of 25-day-old pups and 3-month-old adult animals. Lithium-pilocarpine model of SE was used. Lithium chloride (3 mmol/kg, ip) was injected 24 h before administering pilocarpine (40 mg/kg, ip). This presented study demonstrates the variability of post SE neuronal damage in 25-day-old pups in comparison with 3-month-old adult rats. The NAc exhibited small to moderate number of Fluoro-Jade B (FJB)-positive neurons detected 4 and 8 h post SE intervals. The number of degenerated neurons in the shell subdivision of the NAc significantly increased at survival interval of 12 h after the SE. FJB-positive neurons were evidently more prominent occupying the whole anteroposterior and mediolateral extent of the nucleus at longer survival intervals of 24 and 48 h after the SE. This was also the case in the bordering vicinity between the shell and the core compartments but with clusters of degenerating cells. The severity of damage of the shell subdivision of the NAc reached its peak at an interval of 24 h post SE. Isolated FJB-positive neurons were detected in the ventral peripheral part of the core compartment. Degenerated neurons persisted in the shell subdivision of the NAc 1 week after SE. However, the quantity of cell damage had significantly reduced in comparison with the aforementioned shorter intervals. The third layer of the OT exhibited more degenerated neurons than the second layer. The FJB-positive cells in the young animals were higher than in the adult animals. The morphology of those cells was identical in the two age groups except in the OT.

Heparin-Modified Superparamagnetic Iron Oxide Nanoparticles Suppress Lithium Chloride/Pilocarpine-Induced Temporal Lobe Epilepsy in Rats through Attenuation of Inflammation and Oxidative Stress.

The development of antiepileptic drugs is still a long process. In this study, heparin-modified superparamagnetic iron oxide nanoparticles (UFH-SPIONs) were prepared, and their antiepileptic effect and underlying mechanism were investigated. UFH-SPIONs are stable, homogeneous nanosystems with antioxidant enzyme activity that are able to cross the blood-brain barrier (BBB) and enriched in hippocampal epileptogenic foci. The pretreatment with UFH-SPIONs effectively prolonged the onset of seizures and reduced seizure severity after lithium/pilocarpine (LP)-induced seizures in rats. The pretreatment with UFH-SPIONs significantly decreased the expression of inflammatory factors in hippocampal tissues, including IL-6, IL-1ß, and TNF-α. LP-induced oxidative stress in hippocampal tissues was in turn reduced upon pretreatment with UFH-SPIONs, as evidenced by an increase in the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and a decrease in the level of lipid peroxidation (MDA). Moreover, the LP-induced upregulation of apoptotic cells was decreased upon pretreatment with UFH-SPIONs. Together, these observations suggest that the pretreatment with UFH-SPIONs ameliorates LP-induced seizures and downregulates the inflammatory response and oxidative stress, which exerts neuronal protection during epilepsy.

Lithium chloride promotes mesenchymal-epithelial transition in murine cutaneous wound healing via inhibiting CXCL9 and IGF2.

Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re-epithelialization through mesenchymal-epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal-epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal-derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal-epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal-epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal-epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by ß-catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re-epithelialization in future.

A fresh perspective on dissociation mechanism of cellulose in DMAc/LiCl system based on Li bond theory.

In this case, various characterization technologies have been employed to probe dissociation mechanism of cellulose in N,N-dimethylacetamide/lithium chloride (DMAc/LiCl) system. These results indicate that coordination of DMAc ligands to the Li+-Cl- ion pair results in the formation of a series of Lix(DMAc)yClz (x = 1, 2; y = 1, 2, 3, 4; z = 1, 2) complexes. Analysis of interaction between DMAc ligand and Li center indicate that Li bond plays a major role for the formation of these Lix(DMAc)yClz complexes. And the saturation and directionality of Li bond in these Lix(DMAc)yClz complexes are found to be a tetrahedral structure. The hydrogen bonds between two cellulose chains could be broken at the nonreduced end of cellulose molecule via combined effects of basicity of Cl- ion and steric hindrance of [Li (DMAc)4]+ unit. The unique feature of Li bond in Lix(DMAc)yClz complexes is a key factor in determination of the dissociation mechanism.

Analysis of the effect of cations on protein conformational stability using solid-state nanopores.

The conformation of proteins is closely related to their biological functions, and it is affected by many factors, including the type of cations in solution. However, it is difficult to detect the conformational changes of a protein in situ. As a single-molecule sensing technology, nanopores can convert molecular structural information into analyzable current signals within a reasonable time range. Herein, we detect and analyze the effects of two different types of monovalent cations (Na+ and Li+) on a model protein bovine serum albumin (BSA) conformation using SiNx nanopores with different diameters. The quantitative analysis results show that the excluded volume of BSA in LiCl salt solutions is larger than the value in NaCl solution, indicating that Li+ is more prone to unfolding the proteins and making them unstable. This study demonstrated that nanopores enable the in situ detection of the structure of proteins at the single-molecule level and provide a new approach for the quantitative analysis of proteins.

Neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epilepsy in rats and its underlying mechanisms.

INTRODUCTION: Epilepsy is a common neurological disorder that presents with challenging mechanisms and treatment strategies. This study investigated the neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epileptic rats and explored its potential mechanisms. METHODS: Lithium chloride pilocarpine was used to induce an epileptic model in rats, and the effects of quinpirole on seizure symptoms and cognitive function were evaluated. The Racine scoring method, electroencephalography, and Morris water maze test were used to assess seizure severity and learning and memory functions in rats in the epileptic group. Additionally, immunohistochemistry and Western blot techniques were used to analyze the protein expression levels and morphological changes in glutamate receptor 2 (GluR2; GRIA2), BAX, and BCL2 in the hippocampi of rats in the epileptic group. RESULTS: First, it was confirmed that the symptoms in rats in the epileptic group were consistent with features of epilepsy. Furthermore, these rats demonstrated decreased learning and memory function in the Morris water maze test. Additionally, gene and protein levels of GluR2 in the hippocampi of rats in the epileptic group were significantly reduced. Quinpirole treatment significantly delayed seizure onset and decreased the mortality rate after the induction of a seizure. Furthermore, electroencephalography showed a significant decrease in the frequency of the spike waves. In the Morris water maze test, rats from the quinpirole treatment group demonstrated a shorter latency period to reach the platform and an increased number of crossings through the target quadrant. Network pharmacology analysis revealed a close association between quinpirole and GluR2 as well as its involvement in the cAMP signaling pathway, cocaine addiction, and dopaminergic synapses. Furthermore, immunohistochemistry and Western blot analysis showed that quinpirole treatment resulted in a denser arrangement and a more regular morphology of the granule cells in the hippocampi of rats in the epileptic group. Additionally, quinpirole treatment decreased the protein expression of BAX and increased the protein expression of BCL2. CONCLUSION: The current study demonstrated that quinpirole exerted neuroprotective effects in the epileptic rat model induced by lithium chloride pilocarpine. Additionally, it was found that the treatment not only alleviated the rats' seizure symptoms, but also improved their learning and memory abilities. This improvement was linked to the modulation of protein expression levels of GLUR2, BAX, and BCL2. These findings provided clues that would be important for further investigation of the therapeutic potential of quinpirole and its underlying mechanisms for epilepsy treatment.

Lithium Chloride Effects Field-Induced Protein Unfolding and the Transport Energetics Inside a Nanopipette.

The tapered geometry of nanopipettes offers a unique perspective on protein transport through nanopores since both a gradual and fast confinement are possible depending on the translocation direction. The protein capture rate, unfolding, speed of translocation, and clogging probability are studied by toggling the LiCl concentration between 2 and 4 M. Interestingly, the proteins in this study could be transported with or against electrophoresis and offer vastly different attributes of sensing. Herein, a ruleset for studying proteins is developed that prevents irreversible pore clogging and yields upward of >100,000 events/nanopore. The extended duration of experiments further revealed that the capture rate takes ∼2 h to reach a steady state, emphasizing the importance of reaching equilibrated transport for studying the energetics and kinetics of protein transport (i.e., diffusion vs barrier-limited). Even in the equilibrated transport state, improper lowpass filtering was shown to distort the classification of diffusion-limited vs barrier-limited transport. Finally, electric-field-induced protein unfolding was found to be most prominent in electroosmotic-dominant transport, whereas electrophoretic-dominant events show no evidence of unfolding. Thus, our findings showcase the optimal conditions for protein translocations and the impact on studying protein unfolding, transporting energetics, and acquiring high bandwidth data.

High-performance sulfonated polyether sulfone/chitosan membrane on creatinine transport improved by lithium chloride.

Membrane-based polyether sulfone (PES) is a potential candidate for hemodialysis because of its properties such as high mechanical strength, thermal stability, and chemical resistance. However, the nature of the hydrophobicity in the PES membrane inhibits their performance in transporting creatinine. In this study, polyethersulfone (PES) membranes were modified using a sulfonation process and the addition of chitosan (CS) and lithium chloride (LiCl) to improve its performance in transporting creatinine. The FTIR spectrum of the modified membrane shows peaks of the sulfonate (-SO2), amine (NH), and hydroxyl (-OH) groups in absorption areas of 1065 cm-1, 1650 cm-1, and 3384 cm-1, respectively, indicating that the membrane SPES/CS-LiCl has been successfully prepared. The modified PES membranes shows a higher porosity, swelling, water absorption, and hydrophilicity than pure PES membrane. The modification of the PES membrane in this study also enhances the ability of the membrane to transport creatinine. In the pure PES membrane, the creatinine clearance is 0.30 mg/dL, while in the SPES/CS-LiCl (5:2) membrane the creatinine clearance is 0.42 mg/dL.

Neurotrophin-3 into the insular cortex strengthens conditioned taste aversion memory.

Memory consolidation is an essential process of long-term memory formation. Neurotrophins have been suggested as key regulators of activity dependent changes in the synaptic efficacy and morphology, which are considered the downstream mechanisms of memory consolidation. The neurotrophin 3 (NT-3), a member of the neurotrophin family, and its high affinity receptor TrkC, are widely expressed in the insular cortex (IC), a region with a critical role in the consolidation of the conditioned taste aversion (CTA) paradigm, in which an animal associates a novel taste with nausea. Nevertheless, the role of this neurotrophin in the cognitive processes that the IC mediates remains unexamined. To answer whether NT-3 is involved in memory consolidation at the IC, adult male Wistar rats were administered with NT-3 or NT-3 in combination with the Trk receptors inhibitor K252a into the IC, immediately after CTA acquisition under two different conditions: a strong-CTA (0.2 M lithium chloride i.p.) or a weak-CTA (0.1 M lithium chloride i.p.). Our results show that NT-3 strengthens the memory trace of CTA, transforming a weak conditioning into a strong one, in a Trk-dependent manner. The present evidence suggests that NT-3 has a key role in the consolidation process of an aversive memory in a neocortical region.

Isolation of Double-Stranded RNAs by Lithium Chloride Fractionation.

This procedure provides a comprehensive method for isolating double-stranded RNA (dsRNA) that relies on the different solubility of various nucleic acids in lithium chloride (LiC1). The approach offers several notable advantages including simplicity, avoidance of enzymatic treatments, and the ability to obtain relatively high yields of undegraded dsRNA over other conventional techniques. Moreover, it allows for the separation of different groups of cellular and viral nucleic acids from a single tissue sample. This method was further improved to increase the purity of dsRNA using plant tissues infected by RNA viruses.

Lithium Chloride Promotes Endogenous Synthesis of CLA in Bovine Mammary Epithelial Cells.

Although conjugated linoleic acid (CLA) can promote human health, its content in milk is insufficient to have a significant impact. The majority of the CLA in milk is produced endogenously by the mammary gland. However, research on improving its content through nutrient-induced endogenous synthesis is relatively scarce. Previous research found that the key enzyme, stearoyl-CoA desaturase (SCD) for the synthesis of CLA, can be expressed more actively in bovine mammary epithelial cells (MAC-T) when lithium chloride (LiCl) is present. This study investigated whether LiCl can encourage CLA synthesis in MAC-T cells. The results showed that LiCl effectively increased SCD and proteasome α5 subunit (PSMA5) protein expression in MAC-T cells as well as the content of CLA and its endogenous synthesis index. LiCl enhanced the expression of proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), and its downstream enzymes acetyl CoA carboxylase (ACC), fatty acid synthase (FASN), lipoprotein lipase (LPL), and Perilipin 2 (PLIN2). The addition of LiCl significantly enhanced p-GSK-3ß, ß-catenin, p-ß-catenin protein expression, hypoxia-inducible factor-1α (HIF-1α), and downregulation factor genes for mRNA expression (P < 0.05). These findings highlight that LiCl can increase the expression of SCD and PSMA5 by activating the transcription of HIF-1α, Wnt/ß-catenin, and the SREBP1 signaling pathways to promote the conversion of trans-vaccenic acid (TVA) to the endogenous synthesis of CLA. This data suggests that the exogenous addition of nutrients can increase CLA content in milk through pertinent signaling pathways.

Lipopolysaccharide (LPS) attenuates the primary conditioning of lithium chloride (LiCl)-induced context aversion but not the secondary conditioning of context aversion or taste avoidance.

A first-order association can be formed between toxin-induced nausea and a context, as well as nausea and a taste cue. However, comparatively little is understood about second-order associations. The present study examined if the bacterial endotoxin, LPS, could impair the first- and second-order conditioning of context aversion (anticipatory nausea paradigm) and subsequent conditioned taste avoidance (two-bottle task). Adult male Long Evans rats were treated with LiCl (127 mg/kg, intraperitoneal [i.p.]) or vehicle control (NaCl) and then exposed to a distinct context for 4 first-order conditioning trials. LPS (200 µg/kg, i.p.) or NaCl were administered 24 h after each trial. Seventy-two h after the final first-order conditioning trial, rats underwent 2 second-order conditioning trials where they were treated with 2% saccharin (i.p.) and then exposed to the same context. Twenty-four h after the final second-order conditioning trial, rats were tested in a two-bottle task (2 trials), where they were given a choice between water and a palatable 0.2% saccharin solution. LiCl-treated rats demonstrated a context aversion by the 3rd conditioning trial in the anticipatory nausea paradigm. Rats previously exposed to LiCl also displayed a conditioned taste avoidance of saccharin within the two-bottle task. LPS attenuated first-order context aversion but did not alter either second-order context aversion or conditioned taste avoidance in the two-bottle task. This study demonstrated that a secondary association formed within an aversive context could result in a conditioned taste avoidance. Further, LPS may be able to attenuate primary conditioning, but not secondary conditioning.

Patterns of ingestion of rats during chronic oral administration of lithium chloride.

Chronic lithium administration to rodents is used to explore the potential neural mechanisms of mood stabilization, as well as to model the side effects of chronic lithium on multiple organ systems. Oral administration of lithium in the maintenance diet or drinking water is convenient, but lithium can acutely affect intake and it can mediate acquisition of conditioned taste aversions (CTA). We compared ad libitum food and fluid intake by male rats with LiCl or NaCl solutions as their sole source of fluid across 20 days, with a commonly used dosage of LiCl (24 mM: 1 g / L LiCl). To quantify the pattern of intake, rats were housed in cages equipped with lickometers to detect licks and infrared photobeams to detect food access with 6-s resolution. To determine if rats formed a CTA to LiCl, they were subsequently tested with access to NaCl. Rats showed an immediate avoidance of the LiCl solution, as seen on the first day of access by an increased latency to initiate drinking and a decreased size of drinking bouts. Rats showed a differential response to LiCl vs. NaCl after as few as 5 licks. Chronic consumption of LiCl solution led to significantly decreased food and fluid intake compared to baseline, with concomitant weight loss. The decreased intake was realized by marked changes in the pattern of drinking and feeding bouts: a decrease in per-lick volume and a decrease in licks per drinking bout, and an increase in feeding bout duration resulting in an overall decrease in eating rate. Conversely, chronic NaCl access led to an increase in drinking bout number and licks/bout. The avoidance of LiCl was likely a combination of toxic effects of ingested LiCl and rapid acquisition of a learned aversion to the taste of LiCl, as shown by an extinguishable generalized aversion to NaCl solution during subsequent NaCl test days. The marked effect of chronic oral LiCl on ingestion may impact the oral dosing of lithium as well as the rat's metabolic status.

Activation of multiple neuromodulatory systems in alert rats acquiring conditioned taste aversion revealed by positron emission tomography.

Conditioned taste aversion (CTA) is an essential ability for animals to consume food safely and is regulated by neuromodulatory systems including the dopamine, noradrenaline, serotonin, and acetylcholine systems. However, because few studies focused on a comprehensive understanding of whole-brain activities, how these neuromodulators contribute to the process of CTA remains an open issue. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can visualize activated regions within the whole brain simultaneously and noninvasively. This study aimed to understand the mechanisms of CTA, especially focusing on the retrieval process after CTA acquisition by FDG-PET imaging. CTA was established in rats who received an intraoral application of saccharin solution (IOAS) on the first day (Day 1), a LiCl i.p. injection after an IOAS on Day 2, and an IOAS on Day 3 (CTA group). The subtraction images of Day 3 of the SHAM group, which received a 0.9 % NaCl (saline) injection instead of a LiCl on Day 2, from those of Day 3 of the CTA group revealed increases in FDG signals in multiple brain regions including the substantia nigra, ventral tegmental area, locus coeruleus, dorsal raphe, and nucleus basalis magnocellularis, in addition to the hippocampus and nociception-related regions, including the parabrachial nucleus and solitary nucleus. On the other hand, the visceral pain induced by the LiCl injection increased FDG signals in the primary and secondary somatosensory and insular cortices in addition to the parabrachial nucleus and solitary nucleus. These results suggest that the retrieval process of CTA induces brain regions producing neuromodulators and pain-related brainstem.

Lithium chloride treatments in free flying honey bee colonies: efficacy, brood survival, and within-colony distribution.

The efficacy of various lithium chloride (LiCl) applications in eradicating the parasitic mite Varroa destructor in honey bee colonies was investigated, with a specific focus on its impact on brood development. In broodless colonies (3 weeks post queen caging), the highest efficacy of 98% was achieved with a 9-day treatment of 2.5 kg of candy spiked with 50 mM LiCl. A shorter 5-day treatment with 2 kg of 50 mM LiCl candy resulted in an efficacy of 78%. In colonies with brood, a repeated short-term application of 4 × 0.5 kg 50 mM LiCl candy yielded an efficacy of 88%. LiCl treatment led to a removal of the first batch of brood reared after release of the queen. However, no long-term effects on colony growth were observed, and the colonies successfully overwintered. Additionally, the study demonstrated that lithium is rapidly distributed among the bees of a colony within 2 days, yet only low concentrations were detected in stored food samples. This suggests that the bees efficiently absorb and distribute lithium within the colony. The harvested honey in the following spring revealed a lithium concentration of 0.1-0.2 mg/kg, which is below naturally occurring lithium levels in honey. Based on these findings, LiCl can be considered an effective and easy-to-apply acaricide in broodless colonies, and even in colonies with brood, it had good efficacy and no long-term effects on colony survival. Further research may be necessary to determine the optimal treatment period for achieving an efficacy over 95%.

An evaluation of hedonic responses in taste-potentiated odor aversion using the analysis of licking microstructure and orofacial reactivity.

Two experiments examined the hedonic responses conditioned to odor cues in the phenomenon of taste-potentiated odor aversion. Experiment 1 analyzed the microstructure of licking behavior during voluntary consumption. A tasteless odor (amyl acetate) was delivered to rats either diluted in water or mixed with saccharin before being injected with LiCl. At test, subjects which had received the odor-taste compound during conditioning showed both lower odor consumption and lick cluster size, a result indicating an increased negative evaluation of the odor. Experiment 2 examined the orofacial reactions elicited by the odor as index of its hedonic impact. During conditioning, the rats were intraorally infused with either the odor alone or the odor-saccharin compound before being injected with LiCl. At test, they were infused with the odor and their orofacial responses video recorded. More aversive orofacial responses were elicited by the odor cue in rats that had compound conditioning, again a result indicating a strengthened negative hedonic reactivity compared to animals experiencing odor aversion conditioning alone. Taken together, these results indicate that taste-mediated potentiation of odor aversion conditioning impacts on the acquisition of conditioned hedonic reactions as well as consumption.

Drugs prescribed for Phelan-McDermid syndrome differentially impact sensory behaviors in shank3 zebrafish models.

Background: Altered sensory processing is a pervasive symptom in individuals with Autism Spectrum Disorders (ASD); people with Phelan McDermid syndrome (PMS), in particular, show reduced responses to sensory stimuli. PMS is caused by deletions of the terminal end of chromosome 22 or point mutations in Shank3. People with PMS can present with an array of symptoms including ASD, epilepsy, gastrointestinal distress, and reduced responses to sensory stimuli. People with PMS are often medicated to manage behaviors like aggression and/or self-harm and/or epilepsy, and it remains unclear how these medications might impact perception/sensory processing. Here we test this using zebrafish mutant shank3ab PMS models that likewise show reduced sensory responses in a visual motor response (VMR) assay, in which increased locomotion is triggered by light to dark transitions. Methods: We screened three medications, risperidone, lithium chloride (LiCl), and carbamazepine (CBZ), prescribed to people with PMS and one drug, 2-methyl-6-(phenylethynyl) pyridine (MPEP) tested in rodent models of PMS, for their effects on a sensory-induced behavior in two zebrafish PMS models with frameshift mutations in either the N- or C- termini. To test how pharmacological treatments affect the VMR, we exposed larvae to selected drugs for 24 hours and then quantified their locomotion during four ten-minute cycles of lights on-to-off stimuli. Results: We found that risperidone normalized the VMR in shank3 models. LiCl and CBZ had no effect on the VMR in any of the three genotypes. MPEP reduced the VMR in wildtype (WT) to levels seen in shank3 models but caused no changes in either shank3 model. Finally, shank3 mutants showed resistance to the seizure-inducing drug pentylenetetrazol (PTZ), at a dosage that results in hyperactive swimming in WT zebrafish. Conclusions: Our work shows that the effects of drugs on sensory processing are varied in ways that can be highly genotype- and drug-dependent.

Transition between habits and goal-directed actions in the renewal effect.

Three experiments with rats explored whether previously extinguished goal-directed and habitual responding recover with the same status using an ABA renewal preparation. In Experiments 1a and 1b, a lever-press response was minimally (four sessions) or extensively (16 sessions) trained in one context (Context A) and extinguished in another context (Context B). Then, outcome devaluation took place in either Context A or Context B in which a food pellet reinforcing the response was paired with lithium chloride (LiCl) for devalued groups and with saline for a control group. Finally, renewal of the extinguished response was tested in both Contexts A and B. We confirmed that both minimally and extensively trained responses renewed as goal-directed action regardless of the context in which devaluation took place. This finding was replicated in Experiment 2 even after more extended acquisition training (32 sessions). However, another group that received outcome devaluation before but not after extinction training showed habitual performance during extinction training as well as in a subsequent renewal test. Experiment 3 replicated these results and confirmed that renewal of goal direction for rats that received extinction training immediately prior to outcome devaluation was not an artifact of consecutive LiCl exposures over a short period of time in Experiments 1 and 2, using a more reliable devaluation protocol. Overall, the present results extend previous findings suggesting that actions and habits renew with the same status by returning to the original context after extinction. The most critical finding is the differential effects of pre- and postextinction devaluation on the expression of habitual behavior; extinction prior to devaluation may convert a habitual performance into a goal-directed action. This novel finding is discussed in relation to recent studies that identified several factors contributing to a transition from habitual to goal-directed control of instrumental behavior. (PsycInfo Database Record (c) 2023 APA, all rights reserved).