Acute buspirone abolishes the expression of behavioral dopaminergic supersensitivity in mice

Previous studies have shown that rats withdrawn from long-term treatment with dopamine receptor blockers exhibit dopaminergic supersensitivity, which can be behaviorally evaluated by enhanced general activity observed in an open-field. Recently, it has been reported that co-treatment with the non-benzodiazepine anxiolytic buspirone attenuates the development of haloperidol-induced dopaminergic supersensitivity measured by open-field behavior of rats. The aims of the present study were: 1) to determine, as previously reported for rats, if mice withdrawn from long-term neuroleptic treatment would also develop dopaminergic supersensitivity using open-field behavior as an experimental paradigm, and 2) to examine if acute buspirone administration would attenuate the expression of this behavioral dopaminergic supersensitivity. Withdrawal from long-term haloperidol treatment (2.5 mg/kg, once daily, for 20 days) induced a significant (30%) increase in ambulation frequency (i.e., number of squares crossed in 5-min observation sessions) but did not modify rearing frequency or immobility duration in 3-month-old EPM-M1 male mice observed in the open-field apparatus. Acute intraperitoneal injection of buspirone (3.0 and 10 but not 1.0 mg/kg, 12-13 animals per group) 30 min before open-field exposure abolished the increase in locomotion frequency induced by haloperidol withdrawal. These data suggest that the open-field behavior of mice can be used to detect dopaminergic supersensitivity, whose expression is abolished by acute buspirone administration.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL

Separation and purification of curcumin using novel aqueous two-phase micellar systems composed of amphiphilic copolymer and cholinium ionic liquids

Novel aqueous two-phase micellar systems (ATPMS) composed of Pluronic F68, a triblock amphiphilic copolymer, and cholinium-based ionic liquids (ILs) were formulated and applied for separation/purification of curcumin (CCM). CCM stability in the presence of ATPMS components was also evaluated. CCM is stable up to 24 h in copolymer (1.0 10.0 wt%) and ILs (0.1 3.0 M) aqueous solutions. Very mild phase separation conditions (close to room temperature) were achieved by adding cholinium ILs to the Pluronic F68 + McIlvaine buffer at pH 6.0 solution. The decrease of cloud-point temperature is dependent on the relative hydrophobicity of IL anion, [Hex] > [But] > [Prop] > [Ac] > Cl. ATPMS composed of more hydrophobic ILs ([Ch][Hex] > [Ch][But] > [Ch][Prop]) are most efficient in the partition of commercial CCM into polymeric micelles-rich phase. The best ATPMS (0.70 M [Ch][But] and 0.60 M [Ch][Hex]-based ATPMS) were then used to purify CCM from a crude extract of Curcuma longa L. Both systems were very selective to separate CCM from protein-based contaminants (selectivity values 25; purification yields 12-fold). Pluronic F68-based ATPMS are promising for selective separation of hydrophobic biomolecules by using cholinium-based ILs as adjuvants to adjust phase separation temperatures and biomolecules partition.This study was funded by the Coordination for Higher Level Graduate Improvements (CAPES/Brazil, finance code 001), National Council for Scientific and Technological Development (CNPq/Brazil) and the State of São Paulo Research Foundation (FAPESP/Brazil, processes #2014/16424-7, #2017/10789-1, #2018/10799-0, #2018/05111-9; #2019/05624-9, and #2019/08549-8). A.M. Lopes and J.F.B. Pereira are grateful for the language revision of native speaker H.S. Pacheco Neto.info:eu-repo/semantics/publishedVersio