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4 protocols using way 181187

1

Chronic Effects of APDs and 5-HT6 Ligands

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Haloperidol (TargetMol, Boston, MA, USA), risperidone (TargetMol), olanzapine (TargetMol), WAY-181187 (oxalate; Tocris Bioscience, Bristol, UK), and SB-742457 (TargetMol) were used in the experiment. Doses of APDs (Haloperidol 0.5 mg/kg, risperidone 0.5 mg/kg, and olanzapine 5 mg/kg) and 5-HT6 ligands (WAY-181187 3 mg/kg and SB-742457 3 mg/kg) were selected for the experiments, based on literature review and our previous studies which presented their separate and combined behavioral effects [54 (link)]. The compounds were suspended in a 1% solution of Tween 80 (Sigma Aldrich, St. Louis, MO, USA) immediately before administration and injected intraperitoneally (ip) in a volume of 2 mL/kg. The compounds were dispensed to the rats once daily between 10:00 and 11:00 a.m. for 28 days. The last injection was given 24 h before sacrifice. The control rats received 1% Tween 80, on the same dosing regimen.
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2

Pharmacological Evaluation of Receptor Ligands

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Olanzapine and haloperidol were obtained from FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan). Dopamine hydrochloride and bromocriptine were purchased from Sigma-Aldrich (St Louis, MO, USA). 7-Hydroxy PIPAT, ABT724, TCB2, BW723C86, Ro60–0175, WAY181187, 2-PEA, NGB2904, sonepiprazole, MDL11939, SB204741, SB399885, trans-triprolidine, amthamine, and tiotidine were from Tocris Bioscience (Bristol, England, UK). SB242084 was obtained from Toronto Research Chemicals (Ontario, Canada). All other chemicals used were of the highest purity available.
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3

Electrophysiological Recordings with Neuromodulators

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SB271046 (Purity: ≥99% (HPLC); 5-Chloro-N-[4-methoxy-3-(1-piperazinyl) phenyl]-3-methyl-benzo[b]thiophen-2-sulfonamide hydrochloride; CAS Number: 209481-24-3), WAY181187, and XE991 were obtained from Tocris (Ellisville, MO, USA). The other drugs and reagents were purchased from Sigma (St. Louis, MO, USA). Stock solutions for the drugs mentioned above were DMSO or 0.9% saline solution. All of the drugs tested in electrophysiological recording, including SB-271046 (300nM), WAY-181187 (200nM), NEM (20μM), and XE991 (10μM), were dissolved in artificial cerebral spinal fluid (ACSF) and maintained in slice recording chambers by bath exchange for at least 20 min (West et al., 2009 (link); Zhou et al., 2011 (link)).
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4

Evaluation of Antipsychotic and Selective 5-HT6R Ligands

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The following drugs were used in the study: haloperidol (TargetMol, Boston, MA, USA), risperidone (TargetMol), WAY-181187 (oxalate; Tocris Bioscience, Bristol, UK), and SB-742457 (TargetMol). APDs (haloperidol 0.5 mg/kg and risperidone 0.2 mg/kg) were administered to rats at doses equivalent to the standard ones prescribed for patients with schizophrenia. The equivalent doses were calculated based on the body surface area as described previously by Nair et al.36 (link) Selective 5-HT6R ligands were chosen due to their similar affinity to 5-HT6R (WAY-181187 Ki=2.2 nM22 (link) and SB-742457 Ki=9.6 nM37 (link)), and for comparison reason, these ligands were administered at a dose of 3 mg/kg; ie, a dose at which acute procognitive action for both compounds was observed in our earlier studies.38 (link) The compounds were suspended in a 1% solution of Tween 80 (Sigma Aldrich, UK) before administration and were injected intraperitoneally (ip) in a volume of 2 mL/kg. In the case of acute treatment, haloperidol, risperidone, WAY-181187, and SB-742457 were administered to the rats 60 min before the tests, whereas in the 21-day scheme of treatment, the compounds were administered once a day between 10:00 and 11:00 during 21 consecutive days, with the last injection 24 h before the tests. The control rats were injected with the vehicle according to the same schedule.
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