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2120: Antipsychotic-induced weight gain arises, in part, from alteration of feeding circuitry in the lateral hypothalamic area
- Ryan Michael Cassidy, Hannah Savage, Yungang Lu, Xiang Yang Zhang, Qingchun Tong
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, pp. 1-2
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OBJECTIVES/SPECIFIC AIMS: To demonstrate that olanzapine recapitulates the effect of increased lateral hypothalamic (LH) GABAergic activity in the DRN and the DBB. This will provide a potential neural substrate for the observed increase in consumption of food and weight gain. METHODS/STUDY POPULATION: (1) We will examine electrophysiological activity of the DRN and the DBB in response to optogenetic stimulation of LH fibers to these nuclei. (2) We will identify the behavioral phenotype of stimulating these same projections using optogenetic techniques. (3a) Identify the behavioral phenotype of mice possessing cre-loxp-dependent knockout (KO) of LH GABAergic activity, DRN serotonergic activity, and inhibition of DBB cholinergic activity. (3b) Using these mice, we will establish behavioral response to olanzapine in ad libitum feeding and fast-refeeding condition. (4) Using baseline and post-treatment body mass index (BMI), PANSS, and side effect profile scores from a recently completed prospective cohort study of treatment-naive schizophrenic patients receiving atypical antipsychotics for 1 year, we will sequence multiple single nucleotide polymorphisms and explore the correlation of serotonergic, dopaminergic, and cholinergic receptor mutations with the increase in BMI and changes in PANSS score and side effect scores. RESULTS/ANTICIPATED RESULTS: (1) Our preliminary data indicates that the LH exclusively sends GABAergic input to the DBB, and the large majority of its projections to the DRN are GABAergic. (2) We have identified that stimulating LH–>DBB projections produces intense feeding and drinking behavior, a real-time place preference for laser stimulation, and a conditioned place preference for laser stimulation. Preliminary data shows that the LH->DRN also produces feeding behavior. (3a) Our lab has demonstrated that transgenic mice with LH-specific GABA release KO are smaller, have increased anxiety-like behaviors such a repetitive grooming and open field aversion, and have reduced feeding after fasting conditions. We expect the DRN serotonergic KO mice to have increased body weight and reduced anxiety-like behaviors. (3b) Our pilot study demonstrated that the LH GABA KO mice administered olanzapine have a greater consumption of food over 1 hour than controls (n=7, 5, respectively; p=0.08). DRN serotonergic KO mice and mice with inhibition of choline will have an increased baseline feeding behavior, but will not be affected by olanzapine. (4) We believe that SNPs in serotonergic receptors such as 5HT2C, and those affecting dopaminergic and cholinergic receptors, will be more common in schizophrenic patients with increased BMI than those without. Further, we believe that a reduction in the PANSS items reflecting anxiety and aversiveness will correlate with increased BMI, since we postulate that mimicking LH GABAergic activity will produce its previously demonstrated anxiolytic effects. DISCUSSION/SIGNIFICANCE OF IMPACT: Identifying the important role for a reward-oriented feeding center in the brain in producing antipsychotic weight gain will allow a more comprehensive, ethologically sound approach to behavioral modification therapy in these patients. It will lend mechanistic credence to weight control therapies which have used token economy, opioid antagonism, and other inhibition-promoting therapies. This study will also increase the validity for testing further the use of selective serotonin agonists which prevent weight gain such as lorcaserin.
The conservation status and vocalizations of threatened birds from the scarp forests of the Western Angola Endemic Bird Area
- PETER G. RYAN, IAN SINCLAIR, CALLAN COHEN, MICHAEL S. L. MILLS, CLAIRE N. SPOTTISWOODE, RODNEY CASSIDY
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- Journal:
- Bird Conservation International / Volume 14 / Issue 4 / December 2004
- Published online by Cambridge University Press:
- 25 November 2004, pp. 247-260
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The western Angola Endemic Bird Area has 14 range-restricted species. Little is known about the conservation status of the region's birds due to the civil war that has raged in Angola for the last 27 years. The greatest diversity of restricted-range species is found in Cuanza Sul province, and given the uncertainty about their current status, many of these species are listed as Threatened. In this paper we report the first significant ornithological visits to the Gabela region since 1974. We visited an extensive scarp forest patch at Kumbira Primero, near Conda, as well as smaller forest areas along the Sumbe–Gabela and Sumbe–Seles roads. Most of the threatened species were relocated, including several species not seen since the 1970s. Gabela Bush-shrike Laniarius amboimensis was common and Monteiro's Bush-shrike Malaconotus monteiri was fairly common in degraded secondary forest, old coffee plantations and primary forest at Kumbira. Pulitzer's Longbill Macrosphenus pulitzeri was fairly common at higher elevations at Kumbira as well as in the dense understorey of secondary forest west of Seles. Gabela Akalat Sheppardia gabela was less common, with only three birds found at Kumbira and one near Seles, but may have been overlooked. Only one group of eight Gabela Helmet-shrike Prionops gabela was recorded, in open woodland at the base of the scarp between Kumbira and Seles. Angola Cave-chat Xenocopsychus ansorgei was found on the rocky slopes above the forest at Kumbira. We describe the first sound recordings for five threatened species, which will help future systematic surveys of the region's forests. Vocal evidence confirms the close relationship between Gabela Bush-shrike and Lühder's Bush-shrike L. luehderi. The most pressing need is to assess the extent of remaining forests, map the distribution of key species of conservation concern, and then draft a strategy to conserve key habitat blocks.