Addiction-Related Memory Transfer and Retention in Planaria

Memory retention and transfer in organisms happen at either the neural or genetic level. In humans, addictive behavior is known to pass from parents to offspring. In flatworm planaria (Dugesia tigrina), memory transfer has been claimed to be horizontal, i.e., through cannibalism. Our study is a preliminary step to understand the mechanisms underlying the transfer of addictive behavior to offspring. Since the neural and neurochemical responses of planaria share similarities with humans, it is possible to induce addictions and get predictable behavioral responses. Addiction can be induced in planaria, and decapitation will reveal if the addictive memories are solely stored in the brain. The primary objective was to test the hypothesis that addictive memory is also retained in the brainless posterior region of planaria. The surface preference of the planaria was first determined between smooth and rough surfaces. Through Pavlovian conditioning, the preferred surface was paired with water and the unpreferred surface with sucrose. After the planaria were trained and addicted, their surface preference shifted as a conditioned place preference (CPP) was established. When decapitated, the regenerated segment from the anterior part containing the brain retained the addiction, thus maintaining a shift in the surface preference. Importantly, we observed that the posterior part preserved this CPP as well, suggesting that memory retention is not attributed exclusively to the brain but might also occur at the genetic level. As a secondary objective, the effects of neurotransmitter blocking agents in preventing addiction were studied by administering a D1 dopamine antagonist to planaria, which could provide pointers to treat addictions in humans.

Multifactorial control of gonadotropin release for induction of oocyte maturation: Influence of gonadotropin-releasing hormone, gonadotropin release-inhibiting factor and dopamine receptors in the catfish, Heteropneustes fossilis

Several external and internal factors contribute to the reproductive success of teleosts, which makes the reproductive process complex and unique. In the Indian freshwater catfish, Heteropneustes fossilis, monsoon plays a crucial role as it fine tunes the neuroendocrine axis, culminating in oocyte maturation. Therefore, induction of oocyte maturation requires the coordinated interaction among hypothalamic, hypophyseal, and peripheral hormones. In the present investigation, dual neuroendocrine control of oocyte maturation has been demonstrated in the catfish, H. fossilis. The maturational response in gravid catfish is inhibited in the presence of dopamine but GnRH evokes the oocyte maturation and ovulation. GnRH upregulates the expression of lhb gene as well as increases plasma levels of LH significantly within 30 minutes of its administration. Destruction of the preoptic region in gravid catfish by electrolytic or chemical lesions also causes oocyte maturation and ovulation. But this response is inhibited if dopamine is injected into the nucleus preopticus periventricularis-lesioned fishes. These observations support the role of dopamine as an inhibitory factor, therefore specific receptors of dopamine have been characterized in catfish and their expression in the brain has been quantified. Dopamine receptors are upregulated in dopamine-treated fishes and downregulated if a dopamine antagonist (pimozide) is injected. The present study suggests the presence of inhibitory mechanism for LH secretion in gravid catfish. Abolition of this inhibition is necessary to release LH surge, which in turn stimulates resumption of meiosis and ovulation. Thus peptidergic as well as aminergic systems regulate oocyte maturation in H. fossilis. Neuroendocrine regulation of oocyte maturation and ovulation has major implications for inducing spawning in aquaculture.

Amisulpride: A New Drug for Management of Postoperative Nausea and Vomiting

Objective: To review the pharmacology, efficacy, and safety of amisulpride and determine its role in the management of postoperative nausea and vomiting (PONV). Data Sources: A PubMed search (1946 to November 2020) using the terms amisulpride and APD421 was conducted. Study Selection and Data Extraction: Relevant reports on intravenous amisulpride were included. Data Synthesis: Six clinical trials were evaluated. In 4 trials on the prevention of PONV, a greater percentage of patients who received amisulpride 5 mg compared with placebo experienced a complete response (44%-60% vs 31%-33%, respectively, when used as monotherapy; 58% vs 47%, respectively, when used in combination with another antiemetic). In 2 trials on the treatment of PONV, a significantly greater percentage of patients who received amisulpride 10 mg compared with placebo experienced a complete response (31.4% vs 21.5%, respectively, in patients who had not received prophylaxis; 41.7% vs 28.5%, respectively, in patients who had received prophylaxis). Adverse effects included infusion site pain, chills, hypokalemia, procedural hypotension, and abdominal distension. Relevance to Patient Care and Clinical Practice: Amisulpride is effective for the management of PONV and may be less likely to cause QT prolongation and extrapyramidal symptoms than other dopamine antagonists. Additional information is needed on its use for chemotherapy-induced nausea and vomiting and in children. Conclusions: Amisulpride is an important new option for the multimodal management of PONV in adults, and it may be the preferred dopamine antagonist because of the more favorable safety profile that results from its unique pharmacological properties.

241 Metoclopramide induces low-level hyperprolactinemia to increase milk production in sows

Inadequate milk production by sows often limits the growth rate of piglets. A successful lactation requires prolactin (PRL)-induced differentiation of the alveolar epithelium within the mammary glands of sows between gestation days 90–110 (G90-110). We hypothesized that late gestational hyperprolactinemia in primiparous sows induced by feeding the dopamine antagonist metoclopramide (MET) would enhance mammary epithelial differentiation, milk yield, and piglet growth rate, and that these effects would carry over into a subsequent lactation. Twenty-six gilts were randomly assigned to receive either MET (n = 13, 0.8mg/kg) or vehicle (CON, n = 13) twice daily from G90-110. On G90, circulating PRL levels peaked 45 min after MET dosing (P < 0.001) then returned to baseline 3 h later. This response occurred daily out to G104 (P < 0.05). Treated gilts had increased alveolar lumen diameter on G110 (P < 0.05), though feed intake, body weight, and carcass fat percent were not different during pregnancy or lactation. Piglets born to treated sows had increased body weight and average daily gain on lactation days 14 and 21 (P < 0.05). Piglet milk intake was estimated from deuterium oxide dilution. While milk intake by piglets nursing MET sows was not statistically different from those nursing CON sows on day 21 of lactation (P = 0.18), there was a greater increase in milk consumption by piglets born to MET-treated sows between days 9 and 21 of lactation than for those in CON litters (P < 0.001). In one group of second parity sows, milk yield was increased during their second lactation with no additional treatment (P < 0.05) and their carcass fat dropped by 14% (P < 0.05). These findings demonstrate that MET-induced hyperprolactinemia in pigs during late pregnancy can increase milk yield and piglet growth rate, and this response can be sustained into a second lactation in some sows.

155 Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal transcriptome of gilts

The study objective was to determine the effects of hyperprolactinemia on the mammary parenchymal transcriptome in late-pregnant gilts. Gilts were divided into 3 groups on day 90 of gestation to receive IM injections of 1) canola oil (CTL, n = 18) until day 109 of gestation, 2) domperidone (dopamine antagonist) until day 96 (T7, n = 17) or, 3) domperidone until day 109 (T20, n = 17). Mammary glands were collected on day 110 and parenchymal tissue was sampled for transcriptomic analyses. Total RNA was isolated from 6 CTL and 6 T20 gilts for microarray analysis. The GeneChip® Porcine Gene 1.0 ST Array (19,202 genes) was used for hybridization. Array quality control, data normalization and expression level analyses were performed with the Affymetrix Expression Console and Transcriptome Analysis Console (TAC) software. Using a threshold cut-off of 1.5 fold (P < 0.05), a total of 313 upregulated and 480 downregulated gene transcripts were identified in T20 vs CTL gilts. A qPCR validation analysis of selected upregulated (n = 13) and downregulated (n = 13) genes was conducted on all animals (CTL, T7, T20). The MIXED procedure of SAS was used for statistical analyses. All selected genes were validated for the CTL vs T20 comparison (P < 0.01). Only 4 selected genes (CAMK1G, COL9A1, P2RX7, TDRD1) were downregulated in the T7 treatment (vs CTL, P < 0.05). Functional analyses of differentially expressed genes were performed using the PANTHER classification system. The top upregulated Biological Process enriched GO terms were Inflammatory Response (GO:0006954) and Response to Lipid (GO:0033993). The Positive Regulation of Cell Population Proliferation (GO:0008284) and Regulation of Cellular Catabolic Process (GO:0031329) GO terms were identified for downregulated genes. Results suggest that a sustained hyperprolactinemia during late-pregnancy (T20 treatment) may increase mammary inflammatory response and reduce cell proliferation.

Use of Antipsychotics in Dementia Patients: A Descriptive Study

ABSTRACT Introduction. Dementia is a chronic progressive syndrome in which there is a decrease in the function of cognitive abilities including memory impairment, thinking ability, orientation, understanding, calculation, language, and assessment but without impaired consciousness. Apart from cognitive impairment, dementia is often accompanied by psychological symptoms and behavioural symptoms so that antipsychotic therapy is needed to overcome this. This study aims to identify the description of the use of antipsychotics in patients with dementia at Dr Mohammad Hoesin Palembang in the period 1 January 2014-31 December 2018. Methods. This research was a descriptive study using secondary data in the form of medical records of dementia patients receiving antipsychotic therapy at Dr Mohammad Hoesin General Hospital, Palembang. Samples were taken using a total sampling method. Results. There were 29 dementia patients (38.67%) receiving antipsychotic therapy. Most of the dementia patients who received antipsychotic therapy were in the late elderly age (27.59%) and were female (55.17%). The most commonly administered antipsychotic drug is haloperidol from the dopamine receptor antagonist (60%) with the most frequent dose of 0.5 mg (34.48%). Risperidone from the serotonin-dopamine antagonist class is the second most frequently prescribed antipsychotic drug (34.28%) at a dose of 1 mg (17.28%). The mean of haloperidol was 425 days, and risperidone was 295.5 days. Conclusion. Although in theory, psychological and behavioural symptoms are often found in dementia cases, not all dementia patients in RSUP Dr Mohammad Hoesin Palembang received antipsychotic therapy. People living with dementia who receive antipsychotic treatment get various types of drugs, dosages, and frequencies.

Induced spawning and embryonic development of striped murrel Channa striata (Bloch, 1793) under indoor conditions using salmon gonadotropin releasing hormone analogue (sGnRHa)

Ten successful trials on induced breeding of the striped murrel Channa striata (Bloch, 1793) under indoor conditions were carried out during July-August 2019. Brooders reared in cement tanks,(males weighing in the range of 290-700 g and females 220-600 g), were used in a set of 2:2 male to female ratio for induced breeding with salmon gonadotropin releasing hormone anologue (sGnRHa) and dopamine antagonist commercial formulation. Each brooder set was kept in an FRP tank (13’x3’x14’’) along with submerged macrophyte Hydrilla verticillata, which was sparsely spread all around the tank. Maturity of brooders was screened on the basis of secondary sexual traits. The brooders were given hormonal injection after 6 h of acclimatisation under indoor conditions @ 1 ml kg-1 body weight (containing sGnRHa 20 µg ml-1 and domperidone 10 µg ml-1) to both the sexes. Natural spawning occurred in all ten sets within 21.5+3.2 h (17-26 h) of injection. In all the tanks, two separate egg masses were observed with 30-95% fertilisation. Approximately 0.14 million eggs were scooped out from the tanks and reared in round plastic tanks (70 l) for hatching, where hatching occurred within 17-26 h post-fertilisation (hpf) with hatching rates of 50.76 to 93.18% at 28+2oC. The embryonic development was recorded under a stereo-zoom microscope in live condition under controlled temperature conditions and described with digital images. The study revealed that induced breeding of C. striata can be undertaken in FRP tanks under indoor conditions for mass-scale seed production, which will provide a platform for diversification of this high valued fish species for large scale farming practices in ponds as well a new species for culture in recirculatory aquaculture system (RAS) and biofloc technology (BFT).

S172. GLUTAMATE RELATED CONNECTIVITY DISTURBANCES OF THE SALIENCE AND DEFAULT MODE NETWORKS IN PSYCHOSIS

Background Cortical dysconnectivity and dysfunctional glutamatergic signalling are both implicated in the pathophysiology of psychotic illness. The relationship between these two systems, and the relevance to psychotic disorders remains unknown. Methods 50 individuals with a psychotic disorder and 54 healthy controls received baseline imaging using 1H-MRS to measure anterior cingulate glutamate concentrations, and resting state MRI to characterise functional brain networks. These measures were subsequently repeated following 3 days treatment with either the glutamatergic regulator riluzole (N=36), or a dopamine antagonist (N=14). The network-based statistic was used to examine relationships between glutamate concentrations and connectivity of the salience and default mode networks in patients and controls, and to investigate how this changed following pharmacological manipulation. Results In healthy controls higher baseline anterior cingulate glutamate concentrations were associated with reduced salience network connectivity, particularly for interhemispheric connections. This pattern was not seen in patients, and the greater the divergence from the relationship observed in controls, the greater the severity of negative symptoms. Default mode-salience internetwork connectivity was greater in patients compared to controls, and inversely correlated with baseline glutamate concentrations. Furthermore, riluzole associated changes in glutamate concentrations were associated with an inverse change in internetwork connectivity suggesting a causal relationship. Discussion Individuals with a psychotic disorder showed marked alterations in the relationship between anterior cingulate cortex glutamate concentration and connectivity of the salience and default mode networks. A pharmacological challenge with a glutamate regulating agent modulated this association, highlighting that the relationship is potentially malleable.