Bromocriptine mesylate

Rats were anesthetized through an intraperitoneal injection of ketamine (100 mg per kilogram body weight (BW)) + xylazine (15 mg per kilogram BW). A stereotaxic surgery procedure was employed to implant an intracerebrovascular (ICV) cannula in the lateral ventricle of the hypothalamus (coordinates: 1.3 mm posterior to bregma and 1.9 mm lateral to the midsagittal suture at a depth of 3.5 mm), as previously described [27 (link)]. After this procedure, the animals were individually housed for a 4-day acclimatation period prior to the experiment, allowing them to recover from surgery. The administration of ICV vehicle (DMSO 100 mM), bromocriptine mesylate (40 μg per rat; Tocris, St. Louis, MO, USA), or PF-04455242 hydrochloride (1.39 μg per rat; Tocris, St. Louis, MO, USA) was performed using a 22-gauge needle (Hamilton; Reno, NV, USA) through the implanted cannulas.

The compounds used in the present study were as follows and purchased from Sigma-Aldrich (St. Louis, MO) unless indicated otherwise: D-glucose, dopamine (3-hydroxytyramine HCl), HEPES, sodium pyruvate, penicillin, streptomycin, 2-mercaptoethanol. Human, bovine and porcine insulin were also obtained from Sigma-Aldrich. Rodent (rat/mouse-reactive) insulin was obtained from ALPCO (Salem, NH). Human proinsulin was obtained from R&D Systems (Minneapolis, MN) and human C-peptide was purchased from AnaSpec, EGT (Fremont, CA). Bromocriptine mesylate was purchased from Tocris (Bristol, United Kingdom).

Rats received an acute (24 h) or chronic daily (10 days) intraperitoneal administration (IP) of vehicle (DMSO 100 mM), bromocriptine mesylate (0.625, 1.25, 2.5, 5, 10, and 20 mg/kg per rat; Tocris, St. Louis, MO, USA), or PF-04455242 hydrochloride (0.3125, 0.625, 1.25, 2.5, 5, and 10 mg/kg per rat; Tocris, St. Louis, MO, USA).